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(of)-349.7 (early)-349.7 (embryonic)]TJ T* [(demethylation)-286.6 (followed)-286.6 (by)-286.6 (de)-286.6 (novo)-286.6 (methylation)-286.6 (is)-286.6 (criti-)]TJ T* [(cal)-353.2 (in)-353.2 (determining)-353.2 (somatic)-353.2 (DNA)-353.2 (methylation)-353.2 (patterns.)]TJ T* [(A)-292.6 (genome-wide)-292.6 (reduction)-292.6 (in)-292.6 (methylation)-292.6 (is)-292.6 (also)-292.6 (seen)-292.6 (in)]TJ T* [(primordial)-294.8 (germ)-294.8 (cells)-294.8 (\(Tada)-294.8 (et)-294.8 (al.)-294.8 (1997;)-294.8 (Reik)-294.8 (et)-294.8 (al.)-294.8 (2001\))]TJ T* [(during)-623.1 (the)-623.1 (proliferative)-623.1 (oogonial)-623.1 (and)-623.1 (spermatogonial)]TJ T* (stages.)Tj 1 -1.2222 Td [(The)-326.4 (most)-326.4 (striking)-326.4 (feature)-326.4 (of)-326.4 (vertebrate)-326.4 (DNA)-326.4 (methyl-)]TJ -1 -1.2222 Td [(ation)-451.4 (patterns)-451.4 (is)-451.4 (the)-451.4 (presence)-451.4 (of)-451.4 (CpG)-451.4 (islands,)-451.4 (that)-451.4 (is,)]TJ T* [(unmethylated)-260.7 (GC-rich)-260.7 (regions)-260.7 (that)-260.7 (possess)-260.7 (high)-260.7 (relative)]TJ T* [(densities)-467.2 (of)-467.2 (CpG)-467.2 (and)-467.2 (are)-467.2 (positioned)-467.2 (at)-467.2 (the)-467.2 (5)]TJ /T1_5 1 Tf 21.738 0 Td (\001)Tj /T1_0 1 Tf 0.8002 0 Td [(ends)-467.2 (of)]TJ -22.5381 -1.2222 Td [(many)-340.9 (human)-340.9 (genes)-340.9 (\(for)-340.9 (review,)-340.9 (see)-340.9 (Bird)-340.9 (1987\).)-340.9 (Compu-)]TJ T* [(tational)-485.2 (analysis)-485.2 (of)-485.2 (the)-485.2 (human)-485.1 (genome)-485.2 (sequence)-485.1 (pre-)]TJ T* [(dicts)-227.9 (29,000)-227.9 (CpG)-227.9 (islands)-227.9 (\(Lander)-227.9 (et)-227.9 (al.)-227.9 (2001;)-227.9 (Venter)-227.9 (et)-227.9 (al.)]TJ T* [(2001\).)-517.4 (Earlier)-517.4 (studies)-517.4 (estimated)-517.3 (that)]TJ /T1_3 1 Tf 18.1424 0 Td (\001)Tj /T1_0 1 Tf [(60%)-517.3 (of)-517.4 (human)]TJ -18.1424 -1.2222 Td [(genes)-528.7 (are)-528.7 (associated)-528.7 (with)-528.7 (CpG)-528.7 (islands,)-528.7 (of)-528.7 (which)-528.7 (the)]TJ T* [(great)-285.3 (majority)-285.3 (are)-285.3 (unmethylated)-285.3 (at)-285.3 (all)-285.3 (stages)-285.3 (of)-285.3 (develop-)]TJ T* [(ment)-352.3 (and)-352.3 (in)-352.3 (all)-352.3 (tissue)-352.3 (types)-352.3 (\(Antequera)-352.3 (and)-352.3 (Bird)-352.3 (1993\).)]TJ T* [(Because)-235.2 (many)-235.2 (CpG)-235.1 (islands)-235.2 (are)-235.2 (located)-235.2 (at)-235.2 (genes)-235.2 (that)-235.2 (have)]TJ T* [(a)-593.7 (tissue-restricted)-593.7 (expression)-593.7 (pattern,)-593.7 (it)-593.7 (follows)-593.7 (that)]TJ T* [(CpG)-538.5 (islands)-538.5 (can)-538.5 (remain)-538.5 (methylation-free)-538.5 (even)-538.5 (when)]TJ T* [(their)-382.9 (associated)-382.9 (gene)-382.9 (is)-382.9 (silent.)-382.9 (For)-382.9 (example,)-382.9 (the)-382.9 (tissue-)]TJ T* [(specifically)-365.8 (expressed)-365.8 (human)]TJ /T1_6 1 Tf 14.0402 0 Td (\001)Tj /T1_0 1 Tf [(-globin)-365.8 (\(Bird)-365.8 (et)-365.8 (al.)-365.8 (1987\))]TJ -14.0402 -1.2222 Td (and)Tj /T1_6 1 Tf 1.9337 0 Td (\001)Tj /T1_0 1 Tf 0.8777 0 Td [(2\(1\))-266.7 (collagen)-266.7 (\(McKeon)-266.7 (et)-266.7 (al.)-266.7 (1982\))-266.7 (genes)-266.7 (have)-266.7 (CpG)]TJ -2.8114 -1.2222 Td [(islands)-398.3 (that)-398.4 (remain)-398.3 (unmethylated)-398.3 (in)-398.3 (all)-398.4 (tested)-398.3 (tissues,)]TJ T* [(regardless)-332.7 (of)-332.7 (expression.)]TJ 1 -1.2222 Td [(A)-362.4 (small)-362.4 (but)-362.4 (significant)-362.4 (proportion)-362.4 (of)-362.4 (all)-362.4 (CpG)-362.4 (islands)]TJ -1 -1.2222 Td [(become)-315.6 (methylated)-315.6 (during)-315.6 (development,)-315.7 (and)-315.6 (when)-315.6 (this)]TJ T* [(happens)-318.5 (the)-318.5 (associated)-318.5 (promoter)-318.5 (is)-318.5 (stably)-318.5 (silent.)-318.5 (Devel-)]TJ T* [(opmentally)-245.9 (programmed)-245.9 (CpG-island)-245.9 (methylation)-245.9 (of)-245.9 (this)]TJ T* [(kind)-369 (is)-369 (involved)-369 (in)-369 (genomic)-369 (imprinting)-369 (and)-369 (X)-369 (chromo-)]TJ T* [(some)-286.3 (inactivation)-286.3 (\(see)-286.3 (below\).)-286.3 (The)-286.3 (de)-286.3 (novo)-286.3 (methylation)]TJ 28.6667 72.1111 Td [(events)-303 (occur)-303 (in)-303 (germ)-303 (cells)-303 (or)-303 (the)-303 (early)-303 (embryo)-303 (\(Jaenisch)]TJ T* [(et)-321.3 (al.)-321.3 (1982\),)-321.3 (suggesting)-321.3 (that)-321.3 (de)-321.3 (novo)-321.3 (methylation)-321.3 (is)-321.3 (par-)]TJ T* [(ticularly)-341.2 (active)-341.2 (at)-341.2 (these)-341.2 (stages.)-341.2 (There)-341.2 (is)-341.2 (evidence,)-341.2 (how-)]TJ T* [(ever,)-389.2 (that)-389.2 (de)-389.2 (novo)-389.2 (methylation)-389.2 (can)-389.2 (also)-389.2 (occur)-389.2 (in)-389.2 (adult)]TJ T* [(somatic)-397.1 (cells.)-397.1 (A)-397.1 (significant)-397.1 (fraction)-397.1 (of)-397.1 (all)-397.1 (human)-397.1 (CpG)]TJ T* [(islands)-397.7 (are)-397.7 (prone)-397.7 (to)-397.7 (progressive)-397.7 (methylation)-397.7 (in)-397.7 (certain)]TJ T* [(tissues)-322.9 (during)-322.9 (aging)-322.9 (\(for)-322.9 (review,)-322.9 (see)-322.9 (Issa)-322.9 (2000\),)-322.9 (or)-322.9 (in)-322.9 (ab-)]TJ T* [(normal)-334.3 (cells)-334.3 (such)-334.3 (as)-334.3 (cancers)-334.3 (\(for)-334.3 (review,)-334.3 (see)-334.3 (Baylin)-334.3 (and)]TJ T* [(Herman)-222.8 (2000\))-222.8 (and)-222.8 (permanent)-222.8 (cell)-222.8 (lines)-222.8 (\(Harris)-222.8 (1982;)-222.8 (An-)]TJ T* [(tequera)-353.5 (et)-353.5 (al.)-353.5 (1990;)-353.5 (Jones)-353.5 (et)-353.5 (al.)-353.5 (1990\).)-353.5 (The)-353.5 (rate)-353.5 (of)-353.5 (accu-)]TJ T* [(mulation)-230.1 (of)-230.1 (methylated)-230.1 (CpGs)-230.1 (in)-230.1 (somatic)-230.1 (cells)-230.1 (appears)-230.1 (to)]TJ T* [(be)-487.7 (very)-487.7 (slow.)-487.7 (For)-487.7 (example,)-487.7 (de)-487.7 (novo)-487.7 (methylation)-487.7 (of)-487.7 (a)]TJ T* [(provirus)-547.3 (in)-547.3 (murine)-547.3 (erythroleukemia)-547.3 (cells)-547.3 (took)-547.3 (many)]TJ T* [(weeks)-410.3 (to)-410.3 (complete)-410.3 (\(Lorincz)-410.3 (et)-410.3 (al.)-410.3 (2000\).)-410.3 (Similarly,)-410.4 (the)]TJ T* [(recovery)-519.6 (of)-519.6 (global)-519.6 (DNA)-519.6 (methylation)-519.6 (levels)-519.6 (following)]TJ T* [(chronic)-362 (treatment)-362 (of)-362 (mouse)-362 (cells)-362 (with)-362 (the)-362 (DNA)-362 (meth-)]TJ T* [(ylation)-379.1 (inhibitor)-379.1 (5-azacytidine)-379.1 (required)-379.1 (months)-379.1 (\(Flatau)]TJ T* [(et)-332.7 (al.)-332.7 (1984\).)]TJ 1 -1.2222 Td [(How)-593.1 (do)-593.1 (patterns)-593.1 (of)-593.1 (methylated)-593.1 (and)-593.1 (unmethylated)]TJ -1 -1.2222 Td [(mammalian)-532.5 (DNA)-532.5 (arise)-532.5 (in)-532.5 (development)-532.5 (and)-532.5 (how)-532.5 (are)]TJ T* [(they)-313.4 (maintained?)-313.4 (Why)-313.4 (are)-313.4 (CpG)-313.4 (islands)-313.4 (usually,)-313.4 (but)-313.4 (not)]TJ T* [(always,)-446.3 (methylation-free?)-446.3 (What)-446.3 (causes)-446.3 (methylation)-446.3 (of)]TJ T* [(bulk)-546.4 (non-CpG-island)-546.4 (DNA?)-546.4 (These)-546.4 (burning)-546.4 (questions)]TJ T* [(cannot)-278.1 (be)-278.1 (answered)-278.1 (definitively)-278.1 (at)-278.1 (present,)-278.1 (but)-278.1 (there)-278.1 (are)]TJ T* [(distinct)-232.3 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All Rights Reserved.Universal News w. Commercial Pi 97UniversalUniversal-NewswithCommPi ^ti*n_=fGwIxm@2[ = ^ t @ | @-*Iz Pt s:]>$I[0FXj !!","N"~"""# ###:$%/%%Z3շݷ˷@շշ@ް,Ӭׯ{z+ {z ǩm: `) xPap0׬RCFhQ@ Ct}{{{}tC ް@h@Z#O.@bkz{r*`{rxzz 4224Y(# vgzxrրrla.OA24-#saQDZg$$@$3zbllbbllbbllbbllb*Z*3l3\38DD3D3,887GG77GG7e__de``dlwilYP.6ZCm D##DK4 wg{mZ6.PA/7-|\3bYg.._sqdu}WeU_sqdu}We_ȫyɫ#%l2Eã`V2P-jmON-TD\D\mƣ}zZH0π>*oEm`, $CC׷fvJM_AB<,N~hǾE޶k^3F%Ddx8WwWSOTv˺4枴xa]z}VI2!-7EЦTEP+MM+P()W׷9X//>'';>**;@( ((9' '(,9(uģƣ0 xAO m9.:ncW_7M*bo й«Ip.Lb7h{Bf$ A!$l),zTK\+ V!AL ax>VV=.9(\=<EH#w0ya?}T`d{oѷƵ'0'VPEYhXU 0,zz}}}zz,0 Uh_m_X@`x`O3>::>#3"OC`5M4Nԩ֭}cPDXdu::# >$2$ I.MN?>PN,TD\D\]ohfmzifvhwq{lfm6'';>**;vZZMMMM @ f Y  ;'@jj @jj%% %%j/@j j/@j'o;'Y 'W^>>2WmU (]lXmO;2U (]0W>'иT>!53)bTaTeTeab)5_>I$&`$L.JYkQk\rjpprkYJ.L=)_W_M\\M\\\00\000[[otrqqrtoײotrqqrtootrqqrtoWް԰ 7S.-RR.-SS.-RR.-S>==>>==>j>8*6E"1ڹAThiU=gػj]ϳbɩn  ,-,-ą\SIV\+(_λ̕\iswi]oիxjJ9$=PP=$$ZggZ$W˩x{motkQPt  ,-,-2Q l>" }{ Dedz*äs4!@nB79Vup|ksAgM\\sFErrFEssFErrFEs[21ZZ21[[21ZZ21[W԰-M %_&~2ŐM.PKˠsi^osF3}S.-RR.-SS.-RR.-S>==>>==>uũݩ|󥝥qӈ~Zgu{ s}y}d:6$>#=KpyggxЏyk`qlj xz{Yvʏ~|{yauݱ @mK3q5[h{ vK9<myGWFBۄ~lv~|v bQszzrr~lpvv uskerrlrrdO퍞Zm<%{zWlޯI&PnD9DD9DNEccEaNNEaccENlCO^K^Euũݩ|󟻥@@R ݡ~ʇx ǍyЇpK=#>$}t6@u:dw}yugZk@@~CA`ݓ†c\{ Hupzth@@[swymZ퉈tuzOdrr rreksuJvvplrrs ޘے~|FWGyqly|m%z{v\\V0ŷV0_0n0_0WYʝWҝ~mu-q5rp ^#7hr$`w Zylx:ak}$_mFrN$3%:ysIHIIss5g 4J"yxQb_ .5ĺOp0UmG]uNZ'xD2i ZBl7cF0"SDIuvhcFMv/^t^ɫyk#PtaYHcpI㦜~mervMN#* .JҢzvT{j_ $" $;EߺayìKP[ f0VBRj,QڭmmUKVIfvvp_[[ ^2_Q766A?31E6E6GyQE_9iiN:$ZggZ$WBj:L]X3FaCa-{xKqi{eYQrm{nN4Ŏmve{eme[rN:{z$ZggZ$`:N$ZggZ$RJRr\dedededetLMuuLMttLMuuLMtlw+N+>I$&`$L.JYkQk\rjpprkYJ.L=)_W_MMY'Wܰ԰)vz{_R0*'ĶѯwXpZaO/aٹ@A=rS.-RR.-SS.-RR.-S>==>>==>ϣƩ;}{sh:WE>@HܹizhreNpﱬá\\(  ,-,-`:Nk$ZggZ$ΧvЩ eÙ̩/ ku^Pco{zyv_Pk?{zWzmesnookbnY  ,-,-nb:Ub:k*{KMsFErrFEssFErrFEsW>7԰I `ݧ`tѩo[Kgt>iwS.-RR.-SS.-RR.-S>==>>==>Z`La@ītA9uǞsTzvxa[rݫ,KbsˊggKh GQSEESQGWlF:LZ3FaCa-{xKqi{eYQrm{nNWD9DD9DNEccEaNNEaccEN߲Ŏmve{eme[r+..ahi``ihaotrqqrto;otrqqrto;otrqqrtoV0V0J00J0NNѣ3Z)D2v\Z33rddd|drddpd|dRJR?KkOhddph|d|dhddh|dd`?X}X}X@EV8V.Esw5iobsw@itǨ).g8g@us^n)tO᭧wrrwws@@bo5On^@suwsfEV8V.E"sw5iobsw1itǨ).g8gus^n)tO᭧wrrwwsbo5On^@suwsfEV8V.Esw5iobswitǨ).g8gHus^n)tO᭧wrrwwsDbo5On^@suwsu::# >$2$ I.MN?>PN,TD\D\))i(b/b/g(=P+MM+P()RJR?KkOw|  endstream endobj 57 0 obj << /BaseFont /MathematicalPi-One /Encoding 58 0 R /FirstChar 1 /FontDescriptor 59 0 R /LastChar 5 /Subtype /Type1 /Type /Font /Widths [ 611 611 444 611 556 ] >> endobj 58 0 obj << /Differences [ 1 /H9251 /H9252 /H9256 /H9257 /H9260 ] /Type /Encoding >> endobj 59 0 obj << /Ascent 0 /CapHeight 0 /Descent 0 /Flags 4 /FontBBox [ -30 -210 1000 779 ] /FontFile3 60 0 R /FontName /MathematicalPi-One /ItalicAngle 0 /StemV 46 /Type /FontDescriptor >> endobj 60 0 obj << /Subtype /Type1C /Length 11786 >> stream MathematicalPi-One; mf| z-} #).49>CHNTY^cint{ ")07<AFKQV[binsx~ %+06<AGNSY^elrw} H9009H11001H11084HS11091H9260H9271H11125H9014H11002H9284H9256H9262H9010H11003H11270H5009H9276H9011H11004H6036H11341HV11091H11034H9012H11005H9274H9281H11349H5007HS11349H11032H9013H11006H11350H9254H11008HS11017H9022H11033H9015H11007H11017H9280H9052H9020H9263HV11017H9024H9016H5037H11351H9006HS11005HV11349HS11084H9259H9265H9008H7001H11711H7002H9278HV11084HS11350H9264H9266H9017H11379H11009H11088H9253HV11350HS11021H9001H9251H9257H9018H9002H11356H9277H9267H9252H9269H9261H9023H11091H11407H9019HS11022HS11088H9255H9268H9004H11124H11080H11612H11128H9270H33355H9005H11271H11021H9258H33356HV11005H9021H11630H9275HV11021HV33783H11083H9003H11022HV11022H9282H9272H5008H9007H11408HV11088H9273Copyright (c) 1990 Adobe Systems Incorporated. All Rights Reserved.Mathematical Pi 1Mathematical PiMathematicalPi-One ^{E?}PFgLlCqUwg  i J j - f G w 3 $# Z`t=n5.$xV?d%A $ V !H!","##w#$1$%%[%& &?&v&'l@@_@R(q(Xv$׊tczvdyRxSxSxTg_t̳xugTkbbvyÞtƝȬiRE^Xjj(22)7BrYD6]Uӹ6,,<&&,<,,],ӹ,66,<]&&],<,,,6,D,<&&,<~,,,,6,,<&&,<=ˣ\TQpB/""IOpbYNjs\7,7s, 6,D+7$sca{\7P7J]_~wb0,<&&,<i,6`+ɻ%CFYPZZW K_AA*,<,<]&&,6f,<,<]&&e=ˣ\TQpB/""IOpbYsJ,N,@_+#a,8,,@+#,8,,a <[<I|rmwp\JI|rmwp\JI|rmwp\,]\,݁(r((\w\<I|rmwp\I|rmwp\]] [] 4hjhi `pttppttppttppttpg []F]ݹ[]b==]=]Yݹ[] ===]=]J``:rT\úº]SS\]TcJ>>JK==K\w3 <I|rmwp\v^^ ej:5t~o`O8KUPULP4~rsstXZx×Ӭyyxyth;Gy}-$*r~xf\gaooNjnw\(n!gq6,,?_/,@+#,8فfTv,6,?,?,,@_+#a,8:mjjmmjjm@]@@f((]u=)ucu9m;~HlH3m$PNj֩ ,\m 4m 8 '2,Z q_ bhb*˩ǧxsA~{HDtFNwf0Cz>1m1>C0s]tDH{f*~sAJyZmNjfwfTvNjϩǩ 3ds+{8p9<Ϩk0s5ik5n ~Fm 4m?*WW\m+)~&^D?@X'3m4A?D'([7G HB У2 rPm 2m?ة00m3 mm 5mn $ m $m?n\$nW}Hnz9nX|Co{H{7y0nz;6n g-,mXmm -m``1z-OF1m>HuH@mm/ >z6.m+ sNOxm 'm? d(h5Ppmfm 0m?>(_FORE__EROF_6c$X[#66#[Xc$6? 0 0m3 Qm 5m?ݩHH3m1Hm _FORE__EROF_6c$X[#66#[Xc$6Njک'0 )9m 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?](>];_;2XMd_abdi]esxÐܺ<BKΧlr~n_`uڊyvj{j\osbL`VdtCRf\?tkIEf  endstream endobj 61 0 obj [ 62 0 R 64 0 R ] endobj 62 0 obj << /A 63 0 R /Border [ 0 0 0 ] /Rect [ 200.6 804 271.968 814 ] /Subtype /Link /Type /Annot >> endobj 63 0 obj << /S /URI /URI (http\072\057\057genesdev\056cshlp\056org\057) >> endobj 64 0 obj << /A 65 0 R /Border [ 0 0 0 ] /Rect [ 396.712 804 530.312 814 ] /Subtype /Link /Type /Annot >> endobj 65 0 obj << /S /URI /URI (http\072\057\057www\056cshlpress\056com) >> endobj 66 0 obj << /Length 14801 >> stream BT /GS0 gs /T1_0 1 Tf 8.9802 0 0 8.9802 75.5688 726.8286 Tm [(failure)-452.3 (of)-452.3 (maintenance)-452.3 (was)-452.3 (estimated)-452.3 (to)-452.3 (occur)-452.3 (with)-452.3 (a)]TJ 0 -1.2222 TD [(frequency)-353.2 (of)]TJ /T1_1 1 Tf 6.1513 0 Td (\001)Tj /T1_0 1 Tf [(5%)-353.2 (per)-353.2 (CpG)-353.2 (site)-353.2 (per)-353.2 (cell)-353.2 (division.)-353.2 (Quan-)]TJ -6.1513 -1.2222 Td [(titative)-659.4 (studies)-659.4 (of)-659.4 (an)-659.4 (endogenous)-659.4 (CpG)-659.4 (site)-659.4 (broadly)]TJ T* [(agreed)-306.2 (with)-306.2 (this)-306.2 (figure)-306.2 (\(Riggs)-306.2 (et)-306.2 (al.)-306.2 (1998\).)-306.2 (Cell)-306.2 (clones)-306.2 (in)]TJ T* [(which)-622.1 (this)-622.1 (site)-622.1 (was)-622.1 (initially)-622.1 (unmethylated)-622.1 (acquired)]TJ T* [(methylation)-477.3 (and)-477.3 (clones)-477.3 (where)-477.3 (it)-477.3 (was)-477.3 (methylated)-477.3 (lost)]TJ T* [(methylation.)-369.6 (The)-369.6 (rate)-369.6 (of)-369.6 (change)-369.6 (was)-369.6 (estimated)-369.6 (at)]TJ /T1_1 1 Tf 23.8996 0 Td (\001)Tj /T1_0 1 Tf (4%)Tj -23.8996 -1.2222 Td [(per)-375.6 (cell)-375.6 (generation.)-375.6 (Error)-375.6 (rates)-375.6 (of)-375.6 (this)-375.6 (magnitude)-375.6 (mean)]TJ T* [(that)-246.5 (a)-246.5 (detailed)-246.5 (methylation)-246.5 (pattern)-246.5 (would)-246.5 (eventually)-246.5 (be-)]TJ T* [(come)-593.7 (indistinct)-593.7 (as)-593.7 (cells)-593.7 (proliferate.)-593.7 (Indeed,)-593.7 (dynamic)]TJ T* [(changes)-349.7 (in)-349.7 (detailed)-349.7 (methylation)-349.7 (patterns)-349.7 (have)-349.7 (been)-349.7 (ob-)]TJ T* [(served)-312.8 (in)-312.8 (monoclonal)-312.8 (lyomyomas)-312.8 (\(Silva)-312.8 (et)-312.8 (al.)-312.8 (1993\))-312.8 (and)]TJ T* [(at)-302.4 (the)-302.4 (methylated)]TJ /T1_2 1 Tf 8.574 0 Td (FMR1)Tj /T1_0 1 Tf 3.0803 0 Td [(gene)-302.4 (\(St)]TJ /T1_3 1 Tf [0.1 (\366)]TJ /T1_0 1 Tf [(ger)-302.4 (et)-302.4 (al.)-302.4 (1997\).)-302.4 (These)]TJ -11.6544 -1.2222 Td [(studies)-469.4 (established)-469.4 (that)-469.4 (clonal)-469.4 (populations)-469.4 (of)-469.4 (cells)-469.4 (do)]TJ T* [(not)-500.6 (have)-500.6 (the)-500.6 (homogeneous)-500.6 (methylation)-500.6 (patterns)-500.6 (that)]TJ T* [(would)-347.5 (be)-347.5 (predicted)-347.5 (by)-347.5 (the)-347.5 (replication)-347.5 (model)-347.5 (of)-347.5 (mainte-)]TJ T* [(nance)-269.6 (methylation.)-269.6 (Not)-269.6 (only)-269.6 (does)-269.6 (DNA)-269.6 (methyltransfer-)]TJ T* [(ase)-258.2 (fail)-258.2 (to)-258.2 (complete)-258.2 (half-methylated)-258.2 (sites)-258.2 (at)-258.2 (a)-258.2 (significant)]TJ T* [(rate,)-340.9 (but)-340.9 (also)-340.9 (significant)-340.9 (de)-340.9 (novo)-340.9 (methylation)-340.9 (occurs)-340.9 (at)]TJ T* [(unmethylated)-332.7 (sites.)]TJ 1 -1.2222 Td [(At)-341.2 (first)-341.2 (sight,)-341.2 (these)-341.2 (findings)-341.2 (appear)-341.2 (to)-341.2 (undermine)-341.2 (the)]TJ -1 -1.2222 Td [(concept)-365.8 (of)-365.8 (maintenance)-365.8 (methylation,)-365.8 (but)-365.8 (this)-365.8 (does)-365.8 (not)]TJ T* [(follow.)-278.7 (Although)-278.7 (detailed)-278.7 (methylation)-278.7 (patterns)-278.7 (may)-278.7 (not)]TJ T* [(be)-401.8 (maintained)-401.8 (at)-401.8 (the)-401.8 (level)-401.8 (of)-401.8 (a)-401.8 (single)-401.8 (CpG)-401.8 (nucleotide,)]TJ T* [(the)-403.4 (methylation)-403.4 (status)-403.4 (of)-403.4 (DNA)-403.4 (domains)-403.4 (appears)-403.4 (to)-403.4 (be)]TJ T* [(faithfully)-399 (propagated)-399 (during)-399 (development)-399 (\(Pfeifer)-399 (et)-399 (al.)]TJ T* 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(absence)-244 (of)-244 (the)-244 (only)-244 (known)-244 (maintenance)-244 (DNA)-244 (meth-)]TJ T* [(yltransferase,)-627.8 (DNMT1)-627.8 (\(Rhee)-627.8 (et)-627.8 (al.)-627.8 (2000\).)-627.8 (A)-627.8 (similar)]TJ T* [(phenomenon)-254.7 (may)-254.7 (account)-254.7 (for)-254.7 (the)-254.7 (maintenance)-254.7 (of)-254.7 (allele-)]TJ T* [(specific)-546.1 (DNA)-546.1 (methylation)-546.1 (imprints)-546.1 (under)-546.1 (conditions)]TJ T* [(where)-286.9 (the)-286.9 (concentration)-286.9 (of)-286.9 (DNMT1)-286.9 (is)-286.9 (severely)-286.9 (limiting)]TJ T* [(\(Jaenisch)-332.7 (1997\).)]TJ /T1_4 1 Tf 0 -3.0556 TD [(De)-332.7 (novo)-332.7 (DNA)-332.7 (methylation)-332.7 (by)-277.8 (default?)]TJ /T1_0 1 Tf 0 -1.8333 TD [(The)-264.8 (origin)-264.8 (of)-264.8 (DNA)-264.8 (methylation)-264.8 (patterns)-264.8 (is)-264.8 (a)-264.8 (long-stand-)]TJ 0 -1.2222 TD [(ing)-257.9 (mystery)-257.9 (in)-257.9 (the)-257.9 (field.)-257.9 (The)-257.9 (de)-257.9 (novo)-257.9 (methyltransferases)]TJ T* [(DNMT3A)-333.3 (and)-333.3 (DNMT3B)-333.3 (\(Okano)-333.3 (et)-333.3 (al.)-333.3 (1998a,)-333.3 (1999\))-333.3 (are)]TJ T* [(highly)-222.8 (expressed)-222.8 (in)-222.8 (early)-222.8 (embryonic)-222.8 (cells,)-222.8 (and)-222.8 (it)-222.8 (is)-222.8 (at)-222.8 (this)]TJ T* [(stage)-222.5 (that)-222.5 (most)-222.5 (programmed)-222.5 (de)-222.5 (novo)-222.5 (methylation)-222.5 (events)]TJ T* [(occur.)-469.1 (What)-469.1 (determines)-469.1 (which)-469.1 (regions)-469.1 (of)-469.1 (the)-469.1 (genome)]TJ T* [(should)-299.2 (be)-299.2 (methylated?)-299.2 (An)-299.2 (extreme)-299.2 (possibility)-299.2 (is)-299.2 (that)-299.2 (de)]TJ T* [(novo)-464 (DNA)-464 (methylation)-464 (in)-464 (early)-464 (mammalian)-464 (develop-)]TJ T* [(ment)-409.1 (is)-409.1 (an)-409.1 (indiscriminate)-409.1 (process)-409.1 (potentially)-409.1 (affecting)]TJ T* [(all)-340.3 (CpGs.)-340.3 (Compatible)-340.3 (with)-340.3 (the)-340.3 (default)-340.3 (model)-340.3 (is)-340.3 (the)-340.3 (ap-)]TJ T* [(parent)-297.7 (absence)-297.7 (of)-297.7 (intrinsically)-297.7 (unmethylatable)-297.7 (DNA)-297.6 (se-)]TJ T* [(quences)-575.4 (in)-575.4 (mammalian)-575.4 (genomes.)-575.4 (Even)-575.4 (CpG)-575.4 (islands,)]TJ T* [(most)-340.6 (of)-340.6 (which)-340.6 (are)-340.6 (unmethylated)-340.6 (at)-340.6 (all)-340.6 (times)-340.6 (in)-340.6 (normal)]TJ T* [(cells,)-528.7 (can)-528.7 (acquire)-528.7 (methylation)-528.7 (under)-528.7 (special)-528.7 (develop-)]TJ T* [(mental)-399.6 (circumstances)-399.6 (or)-399.6 (in)-399.6 (abnormal)-399.6 (cells)-399.6 (\(permanent)]TJ T* [(cell)-243 (lines)-243 (or)-243 (cancer)-243 (cells\).)-243 (It)-243 (is)-243 (clear,)-243.1 (however,)-243 (that)-243 (not)-243 (all)]TJ T* [(regions)-479.8 (of)-479.8 (the)-479.8 (genome)-479.8 (are)-479.8 (equally)-479.8 (accessible)-479.8 (to)-479.8 (DNA)]TJ 28.6667 72.1111 Td [(methyltransferases.)-325.4 (DNMT3B)-325.4 (in)-325.4 (particular)-325.4 (is)-325.4 (known)-325.4 (to)]TJ T* [(be)-306.2 (required)-306.2 (for)-306.2 (de)-306.2 (novo)-306.2 (methylation)-306.2 (of)-306.2 (specific)-306.2 (genomic)]TJ T* [(regions,)-320.4 (as)-320.4 (mice)-320.4 (or)-320.4 (human)-320.4 (patients)-320.4 (with)-320.4 (DNMT3B)-320.4 (mu-)]TJ T* [(tations)-399.3 (are)-399.3 (deficient)-399.3 (in)-399.3 (methylation)-399.3 (of)-399.3 (pericentromeric)]TJ T* [(repetitive)-472.8 (DNA)-472.8 (sequences)-472.8 (and)-472.8 (at)-472.8 (CpG)-472.8 (islands)-472.8 (on)-472.8 (the)]TJ T* [(inactive)-247.5 (X)-247.5 (chromosome)-247.5 (\(Miniou)-247.5 (et)-247.5 (al.)-247.5 (1994;)-247.5 (Okano)-247.5 (et)-247.5 (al.)]TJ T* [(1998b;)-283.8 (Hansen)-283.8 (et)-283.8 (al.)-283.8 (2000;)-283.8 (Kondo)-283.8 (et)-283.8 (al.)-283.8 (2000\).)-283.8 (DNMT3B)]TJ T* [(may)-340.6 (therefore)-340.6 (be)-340.6 (adapted)-340.6 (to)-340.6 (methylate)-340.6 (regions)-340.6 (of)-340.6 (silent)]TJ T* (chromatin.)Tj 1 -1.2222 Td [(Evidence)-326.7 (that)-326.7 (accessory)-326.7 (factors)-326.7 (are)-326.7 (also)-326.7 (needed)-326.7 (to)-326.7 (en-)]TJ -1 -1.2222 Td [(sure)-269.9 (appropriate)-269.9 (methylation)-269.9 (came)-269.9 (initially)-269.9 (from)-269.9 (plants,)]TJ T* [(where)-452 (the)-452 (SNF2-like)-452 (protein)-452 (DDM1)-452 (was)-452 (shown)-452 (to)-452 (be)]TJ T* [(essential)-890.5 (for)-890.5 (full)-890.5 (methylation)-890.5 (of)-890.5 (the)]TJ /T1_2 1 Tf 20.3955 0 Td (Arabidopsis)Tj -20.3955 -1.2222 Td (thaliana)Tj /T1_0 1 Tf 4.3976 0 Td [(genome)-452.6 (\(Jeddeloh)-452.6 (et)-452.6 (al.)-452.6 (1999\).)-452.6 (An)-452.6 (equivalent)]TJ -4.3976 -1.2222 Td [(dependence)-369.3 (is)-369.3 (seen)-369.3 (in)-369.3 (animals,)-369.3 (as)-369.3 (mutations)-369.3 (in)-369.3 (human)]TJ /T1_2 1 Tf T* (ATRX)Tj /T1_0 1 Tf 3.1547 0 Td [(\(Gibbons)-265.8 (et)-265.8 (al.)-265.8 (2000\))-265.8 (and)-265.8 (mouse)]TJ /T1_2 1 Tf 14.9854 0 Td (Lsh2)Tj /T1_0 1 Tf 2.4877 0 Td [(genes)-265.8 (\(Den-)]TJ -20.6278 -1.2222 Td [(nis)-439.1 (et)-439.1 (al.)-439.1 (2001\),)-439.1 (both)-439.1 (of)-439.1 (which)-439.1 (encode)-439.1 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(chromatin)-260.1 (structure)-260.1 (by)-260.1 (these)-260.1 (chromatin-)]TJ T* [(remodeling)-354.8 (proteins)-354.8 (so)-354.8 (that)-354.8 (DNMTs)-354.8 (can)-354.8 (gain)-354.8 (access)-354.8 (to)]TJ T* [(the)-463.7 (DNA.)-463.7 (Collaboration)-463.7 (between)-463.7 (DNMTs)-463.7 (and)-463.7 (factors)]TJ T* [(that)-381.9 (allow)-381.9 (them)-381.9 (access)-381.9 (to)-381.9 (specialized)-381.9 (chromosomal)-381.9 (re-)]TJ T* [(gions)-361.7 (may)-361.7 (be)-361.7 (particularly)-361.7 (important)-361.7 (in)-361.7 (regions)-361.7 (that)-361.7 (are)]TJ T* [(heterochromatic)-371.5 (and)-371.5 (inaccessible.)-371.5 (Although)-371.5 (the)-371.5 (net)-371.5 (re-)]TJ T* [(sult)-596.3 (of)-596.3 (these)-596.3 (processes)-596.3 (is)-596.3 (apparently)-596.3 (global)-596.3 (genomic)]TJ T* [(methylation,)-278.7 (the)-278.7 (evidence)-278.7 (for)-278.7 (selectivity)-278.7 (means)-278.7 (that)-278.7 (the)]TJ T* (word)Tj /T1_3 1 Tf 2.6666 0 Td (\223)Tj /T1_0 1 Tf (default)Tj /T1_3 1 Tf [0.1 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(1999;)-232.3 (Shemer)-232.3 (et)-232.3 (al.)-232.3 (2000\),)-232.3 (tend)-232.3 (to)-232.3 (retain)-232.3 (their)]TJ T* [(methylation)-223.2 (levels)-223.2 (tenaciously)-223.2 (even)-223.2 (when)-223.2 (the)-223.2 (amount)-223.2 (of)]TJ T* [(the)-397.4 (maintenance)-397.4 (enzyme)-397.4 (DNMT1)-397.4 (is)-397.4 (reduced)-397.4 (\(Beard)-397.4 (et)]TJ T* [(al.)-754.1 (1995\).)-754.1 (The)-754.1 (de)-754.1 (novo)-754.1 (methylases)-754.1 (DNMT3A)-754.1 (and)]TJ T* [(DNMT3B)-416.3 (\(Okano)-416.3 (et)-416.3 (al.)-416.3 (1998a,)-416.3 (1999\))-416.3 (may)-416.3 (be)-416.3 (attracted)]TJ T* [(disproportionately)-454.5 (to)-454.5 (these)-454.5 (sequences,)-454.5 (and)-454.5 (this)-454.5 (attrac-)]TJ T* [(tion)-253.5 (may)-253.5 (also)-253.5 (underlie)-253.5 (the)-253.5 (decision)-253.5 (to)-253.5 (methylate)-253.5 (the)-253.5 (box)]TJ T* [(in)-389.5 (the)-389.5 (first)-389.5 (place.)-389.5 (In)-389.5 (other)-389.5 (words,)-389.5 (de)-389.5 (novo)-389.5 (methylation)]TJ T* [(may)-344.7 (not)-344.7 (occur)-344.7 (once)-344.7 (at)-344.7 (a)-344.7 (discrete)-344.7 (and)-344.7 (perhaps)-344.7 (rather)-344.7 (in-)]TJ T* [(accessible)-286.6 (stage)-286.6 (of)-286.6 (germ-cell)-286.6 (development,)-286.6 (but)-286.6 (may)-286.6 (hap-)]TJ T* [(pen)-326.1 (repeatedly)-326.1 (\(assisted)-326.1 (by)-326.1 (DNMT1\))-326.1 (as)-326.1 (embryonic)-326.1 (cells)]TJ T* (divide.)Tj /T1_2 1 Tf 0 -3.0556 TD [(Unusual)-332.7 (DNA)-332.7 (structures)-332.7 (and)-332.7 (RNAi)-332.7 (as)-332.7 (triggers)]TJ 0 -1.2222 TD [(for)-332.7 (de)-332.7 (novo)-277.8 (methylation)]TJ /T1_0 1 Tf 0 -1.8333 TD [(Studies)-468.7 (of)-468.7 (purified)-468.7 (DNMT1)-468.7 (revealed)-468.7 (that)-468.7 (the)-468.7 (enzyme)]TJ 0 -1.2222 TD [(prefers)-453.3 (to)-453.3 (methylate)-453.3 (unusual)-453.3 (DNA)-453.3 (structures)-453.3 (in)-453.3 (vitro)]TJ T* [(\(Smith)-272.4 (et)-272.4 (al.)-272.4 (1991;)-272.4 (Laayoun)-272.4 (and)-272.4 (Smith)-272.4 (1995\).)-272.4 (This)-272.4 (led)-272.4 (to)]TJ T* [(the)-327 (idea)-327 (that)-327 (such)-327 (structures)-327 (might)-327 (be)-327 (generated)-327 (during)]TJ T* [(recombination)-545.4 (between)-545.4 (repetitive)-545.4 (elements)-545.4 (or)-545.4 (during)]TJ T* [(transposition)-365.5 (events)-365.5 (and)-365.5 (directly)-365.5 (trigger)-365.5 (de)-365.5 (novo)-365.5 (meth-)]TJ T* [(ylation)-416.7 (\(Bestor)-416.7 (and)-416.7 (Tycko)-416.7 (1996\).)-416.7 (Subsequent)-416.7 (evidence,)]TJ T* [(however,)-283.5 (does)-283.4 (not)-283.5 (support)-283.5 (a)-283.4 (role)-283.4 (for)-283.5 (DNMT1)-283.4 (in)-283.4 (de)-283.4 (novo)]TJ T* [(methylation)-537.5 (in)-537.6 (vivo)-537.6 (\(Lyko)-537.6 (et)-537.6 (al.)-537.6 (1999;)-537.6 (Howell)-537.6 (et)-537.6 (al.)]TJ T* [(2001\),)-548.3 (and)-548.3 (therefore)-548.3 (the)-548.3 (biological)-548.3 (significance)-548.3 (of)-548.3 (its)]TJ T* [(predilection)-476.9 (for)-476.9 (deformed)-476.9 (DNA)-476.9 (is)-476.9 (uncertain.)-476.9 (There)-476.9 (is)]TJ T* [(evidence)-339.9 (for)-340 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-1.2222 Td [(ation)-239.3 (field)-239.3 (have)-239.3 (arisen)-239.3 (through)-239.3 (molecular)-239.3 (genetic)-239.3 (studies)]TJ 28.6667 72.1111 Td [(of)-381.3 (posttranscriptional)-381.3 (gene)-381.3 (silencing)-381.3 (in)-381.3 (plants.)-381.3 (Double-)]TJ T* [(stranded)-278.4 (RNA)-278.4 (directs)-278.4 (the)-278.4 (destruction)-278.4 (of)-278.4 (transcripts)-278.4 (con-)]TJ T* [(taining)-341.2 (the)-341.2 (same)-341.2 (sequence,)-341.2 (but)-341.2 (there)-341.2 (is)-341.2 (compelling)-341.2 (evi-)]TJ T* [(dence)-316.9 (that)-316.9 (it)-316.9 (can)-316.9 (also)-316.9 (direct)-316.9 (de)-316.9 (novo)-316.9 (methylation)-316.9 (of)-316.9 (ho-)]TJ T* [(mologous)-732 (genomic)-732 (DNA)-732 (\(Wassenegger)-732 (et)-732 (al.)-732 (1994;)]TJ T* [(Bender)-537.2 (2001;)-537.2 (Matzke)-537.2 (et)-537.2 (al.)-537.2 (2001\).)-537.2 (Posttranscriptional)]TJ T* [(gene)-421.1 (silencing)-421.1 (by)-421.1 (double-stranded)-421.1 (RNA)-421.1 (is)-421.1 (probably)-421.1 (an)]TJ T* [(ancient)-556.5 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(methyl-)]TJ T* [(ation)-247.5 (is)-247.5 (barely)-247.5 (detectable)-247.5 (in)-247.5 (adult)-247.5 (cells)-247.5 (\(Ramsahoye)-247.5 (et)-247.5 (al.)]TJ T* [(2000\).)-493.7 (Plants)-493.7 (have)-493.7 (a)-493.7 (CpG)-493.7 (methylation)-493.7 (system,)-493.7 (but)-493.7 (it)]TJ T* [(does)-437.8 (not)-437.8 (appear)-437.8 (to)-437.8 (be)-437.8 (essential)-437.8 (for)-437.8 (RNA-directed)-437.8 (gene)]TJ T* [(silencing)-659.4 (\(for)-659.4 (reviews,)-659.4 (see)-659.4 (Wassenegger)-659.4 (et)-659.4 (al.)-659.4 (1994;)]TJ T* [(Bender)-333.6 (2001;)-333.6 (Matzke)-333.6 (et)-333.6 (al.)-333.6 (2001\).)-333.6 (Optimism)-333.6 (that)-333.6 (RNA-)]TJ T* [(directed)-424.2 (de)-424.2 (novo)-424.2 (methylation)-424.2 (will)-424.2 (also)-424.2 (apply)-424.2 (in)-424.2 (mam-)]TJ T* [(mals)-327.6 (is)-327.6 (tempered)-327.6 (by)-327.6 (this)-327.6 (sequence)-327.6 (disparity,)-327.6 (and)-327.6 (by)-327.6 (the)]TJ T* [(absence)-285.7 (so)-285.7 (far)-285.7 (of)-285.7 (a)-285.7 (clear)-285.7 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(et)-493.4 (al.)-493.4 (1996;)-493.4 (Wutz)-493.4 (and)-493.4 (Jaenisch)]TJ T* [(2000\).)-243.7 (In)-243.7 (other)-243.7 (words,)-243.7 (methylation)-243.7 (affects)-243.7 (the)-243.7 (X)-243.7 (chromo-)]TJ T* [(some)-451.1 (on)-451.1 (which)-451.1 (genes)-451.1 (are)-451.1 (already)-451.1 (shut)-451.1 (down)-451.1 (by)-451.1 (other)]TJ T* [(mechanisms.)-479.8 (Is)-479.8 (transcriptional)-479.8 (inertia)-479.8 (during)-479.8 (embryo-)]TJ T* [(genesis)-389.5 (the)-389.5 (trigger)-389.5 (for)-389.5 (de)-389.5 (novo)-389.5 (methylation?)-389.5 (Studies)-389.5 (of)]TJ T* [(the)-453.6 (origin)-453.6 (of)-453.6 (methylation-free)-453.6 (CpG)-453.6 (islands)-453.6 (offer)-453.6 (some)]TJ T* [(support)-347.8 (for)-347.8 (this)-347.8 (idea.)-347.8 (The)-347.8 (coincidence)-347.8 (between)-347.8 (CpG)-347.8 (is-)]TJ T* [(lands)-500.6 (and)-500.6 (promoters)-500.6 (is)-500.6 (striking)-500.6 (\(Bird)-500.6 (1987\),)-500.6 (and)-500.6 (foot-)]TJ T* [(printing)-340.3 (shows)-340.3 (that)-340.3 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(2000\),)-287.9 (as)-287.9 (is)]TJ T* [(a)-454.8 (CpG)-454.8 (island)-454.8 (that)-454.9 (covers)-454.9 (exon)-454.8 (2)-454.8 (of)-454.9 (the)-454.8 (class)-454.9 (II)-454.9 (major)]TJ T* [(histocompatibility)-389.2 (gene)-389.2 (\(MacLeod)-389.2 (et)-389.2 (al.)-389.2 (1998\).)-389.2 (The)-389.2 (po-)]TJ T* [(tential)-237.1 (importance)-237 (of)-237 (promoter)-237 (function)-237 (in)-237 (the)-237 (genesis)-237 (of)]TJ T* [(CpG)-237.4 (islands)-237.4 (is)-237.4 (highlighted)-237.4 (by)-237.4 (studies)-237.4 (in)-237.4 (transgenic)-237.4 (mice.)]TJ T* [(CpG-island-containing)-419.8 (transgenes)-419.8 (normally)-419.8 (faithful)-419.8 (re-)]TJ T* [(produce)-399 (their)-399 (methylation-free)-399 (character,)-399 (but)-399 (their)-399 (im-)]TJ T* [(munity)-466.2 (to)-466.2 (methylation)-466.2 (is)-466.2 (lost)-466.2 (if)-466.2 (promoter)-466.2 (function)-466.2 (is)]TJ T* [(impaired)-520.8 (\(Brandeis)-520.8 (et)-520.8 (al.)-520.8 (1994;)-520.8 (MacLeod)-520.8 (et)-520.8 (al.)-520.8 (1994\).)]TJ T* [(Similarly,)-285.3 (viral)-285.3 (DNA)-285.3 (integrated)-285.3 (into)-285.3 (ES)-285.3 (cell)-285.3 (genomes)-285.3 (by)]TJ T* [(homologous)-431.8 (recombination)-431.8 (becomes)-431.8 (methylated)-431.8 (when)]TJ T* [(the)-228.5 (promoter)-228.5 (is)-228.5 (weakened)-228.5 (by)-228.5 (absence)-228.5 (of)-228.5 (an)-228.5 (enhancer,)-228.5 (but)]TJ T* [(excludes)-704.9 (methylation)-704.8 (when)-704.8 (an)-704.8 (enhancer)-704.9 (is)-704.9 (present)]TJ T* [(\(Hertz)-305.9 (et)-305.9 (al.)-305.9 (1999\).)-305.9 (A)-305.9 (parsimonious)-305.9 (interpretation)-305.9 (of)-305.9 (the)]TJ T* [(results)-266.4 (is)-266.4 (that)-266.4 (failure)-266.4 (to)-266.4 (transcribe)-266.4 (invites)-266.4 (de)-266.4 (novo)-266.4 (meth-)]TJ T* [(ylation)-417 (\(see)-417 (Fig.)-417 (2)-417 (below\),)-417 (although)-417 (other)-417 (potential)-417 (ex-)]TJ T* [(planations)-236.7 (\(Brandeis)-236.7 (et)-236.7 (al.)-236.7 (1994;)-236.7 (Mummaneni)-236.7 (et)-236.7 (al.)-236.7 (1998\))]TJ T* [(cannot)-332.7 (be)-332.7 (discounted.)]TJ 1 -1.2222 Td [(The)-524.9 (signal)-524.9 (for)-524.9 (this)-524.9 (putative)-524.9 (gene)-524.9 (silence-related)-524.9 (de)]TJ -1 -1.2222 Td [(novo)-389.8 (methylation)-389.8 (is)-389.8 (unknown,)-389.8 (but)-389.8 (the)-389.8 (possibility)-389.8 (that)]TJ T* [(chromatin)-298 (states)-298 (inform)-298 (the)-298 (DNA)-298 (methylation)-298 (machin-)]TJ T* [(ery)-674.9 (is)-674.9 (attractive)-674.9 (\(Selker)-674.9 (1990\).)-674.9 (The)-674.9 (acetylation)-674.9 (and)]TJ T* [(methylation)-247.5 (state)-247.5 (of)-247.5 (nucleosomal)-247.5 (histones)-247.5 (is)-247.5 (tightly)-247.5 (cor-)]TJ T* [(related)-801.4 (with)-801.4 (transcriptional)-801.4 (activity)-801.4 (\(Jenuwein)-801.4 (and)]TJ T* [(Allis)-438.4 (2001\))-438.4 (and)-438.4 (could)-438.4 (be)-438.4 (read)-438.4 (by)-438.4 (the)-438.4 (methylation)-438.4 (ma-)]TJ T* [(chinery,)-303.3 (leading)-303.3 (it)-303.3 (to)-303.3 (either)-303.3 (methylate)-303.3 (or)-303.3 (fail)-303.3 (to)-303.3 (methyl-)]TJ T* [(ate)-299.2 (a)-299.2 (particular)-299.2 (domain.)-299.2 (Indeed,)-299.2 (recent)-299.2 (work)-299.2 (on)]TJ /T1_1 1 Tf 22.3395 0 Td (Neuros-)Tj -22.3395 -1.2222 Td (pora)Tj /T1_0 1 Tf 2.46 0 Td [(\(Tamaru)-403.1 (and)-403.1 (Selker)-403.1 (2001\))-403.1 (has)-403.1 (shown)-403.1 (an)-403.1 (intimate)]TJ -2.46 -1.2222 Td [(link)-538.2 (between)-538.2 (histone)-538.2 (methylation)-538.2 (and)-538.2 (DNA)-538.2 (methyl-)]TJ T* [(ation)-402.1 (in)-402.1 (that)-402.1 (fungus,)-402.1 (as)-402.1 (mutation)-402.1 (of)-402.1 (a)-402.1 (histone)-402.1 (methyl-)]TJ T* [(transferase)-473.2 (that)-473.2 (methylates)-473.2 (Lys)-473.2 (9)-473.2 (of)-473.2 (histone)-473.2 (H3)-473.2 (abol-)]TJ T* [(ished)-501.2 (genomic)-501.3 (methylation.)-501.3 (In)-501.2 (mammalian)-501.2 (and)-501.2 (yeast)]TJ T* [(systems,)-540.7 (histone)-540.7 (H3)-540.7 (Lys)-540.7 (9)-540.7 (methylation)-540.7 (is)-540.7 (associated)]TJ T* [(with)-432.4 (transcriptionally)-432.4 (repressed)-432.4 (heterochromatin)-432.4 (\(Ban-)]TJ T* [(nister)-444.4 (et)-444.4 (al.)-444.4 (2001;)-444.4 (Nakayama)-444.4 (et)-444.4 (al.)-444.4 (2001;)-444.4 (Noma)-444.4 (et)-444.4 (al.)]TJ T* [(2001;)-444.4 (Zhang)-444.4 (and)-444.4 (Reinberg)-444.4 (2001\).)-444.4 (If)-444.4 (the)-444.4 (dependence)-444.4 (of)]TJ T* [(DNA)-464 (methylation)-464 (on)-464 (prior)-464 (histone)-464 (methylation)-464 (turns)]TJ T* [(out)-507.6 (to)-507.6 (be)-507.6 (applicable)-507.6 (to)-507.6 (mammals,)-507.6 (this)-507.6 (would)-507.6 (further)]TJ T* [(strengthen)-374 (the)-374 (argument)-374 (that)-374 (DNA)-374 (methylation)-374 (is)-374 (tar-)]TJ T* [(geted)-333.6 (to)-333.6 (genes)-333.6 (that)-333.6 (are)-333.6 (already)-333.6 (silent.)-333.6 (The)-333.6 (nature)-333.6 (of)-333.6 (the)]TJ T* [(molecular)-327 (cues)-327 (that)-327 (trigger)-327 (transfer)-327 (of)-327 (methyl)-327 (groups)-327 (to)]TJ T* [(unmethylated)-436.2 (DNA)-436.2 (should)-436.2 (be)-436.2 (illuminated)-436.2 (by)-436.2 (ongoing)]TJ T* [(studies)-519.6 (of)-519.6 (multiprotein)-519.6 (complexes)-519.6 (that)-519.6 (contain)-519.6 (DNA)]TJ T* [(methyltransferases)-302.1 (\(Fuks)-302.1 (et)-302.1 (al.)-302.1 (2000,)-302.1 (2001;)-302.1 (Robertson)-302.1 (et)]TJ 28.6667 72.1111 Td [(al.)-364.6 (2000;)-364.6 (Bachman)-364.6 (et)-364.6 (al.)-364.6 (2001\))-364.6 (and)-364.6 (the)-364.6 (identification)-364.6 (of)]TJ T* [(genes)-357.9 (that)-357.9 (modify)-357.9 (DNA)-357.9 (methylation)-357.9 (patterns)-357.9 (\(Weng)-357.9 (et)]TJ T* [(al.)-332.7 (1995\).)]TJ /T1_3 1 Tf 0 -3.0555 TD [(Consequences)-332.7 (of)-332.7 (methylation)-332.7 (gain:)-332.7 (stable)]TJ 0 -1.2222 TD [(transcriptional)-332.7 (silencing)-332.7 (of)-277.8 (genes)]TJ /T1_0 1 Tf 0 -1.8333 TD [(Why)-244 (methylate)-244 (genes)-244 (that)-244 (are)-244 (already)-244 (silent?)-244 (A)-244 (plausible)]TJ 0 -1.2222 TD [(answer)-639.8 (is:)-639.8 (to)-639.8 (silence)-639.8 (them)-639.8 (irrevocably.)-639.8 (Methylation)]TJ T* 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[(quences,)-278.4 (and)-278.4 (some)-278.4 (of)-278.4 (these)-278.4 (fail)-278.4 (to)-278.4 (bind)-278.4 (when)-278.4 (the)-278.4 (CpG)-278.4 (is)]TJ T* [(methylated.)-593.1 (Strong)-593.1 (evidence)-593.1 (for)-593.1 (involvement)-593.1 (of)-593.1 (this)]TJ T* [(mechanism)-251.2 (in)-251.2 (gene)-251.3 (regulation)-251.3 (comes)-251.3 (from)-251.2 (studies)-251.3 (of)-251.3 (the)]TJ T* [(role)-358.6 (of)-358.6 (the)-358.6 (CTCF)-358.6 (protein)-358.6 (in)-358.6 (imprinting)-358.6 (at)-358.6 (the)]TJ /T1_1 1 Tf 21.8938 0 Td (H19)Tj /T1_0 1 Tf (/)Tj /T1_1 1 Tf (Igf2)Tj /T1_0 1 Tf -21.8938 -1.2222 Td [(locus)-261.7 (in)-261.7 (mice)-261.7 (\(Bell)-261.7 (and)-261.7 (Felsenfeld)-261.7 (2000;)-261.7 (Hark)-261.7 (et)-261.7 (al.)-261.7 (2000;)]TJ T* [(Szabo)-350.1 (et)-350.1 (al.)-350.1 (2000;)-350.1 (Holmgren)-350 (et)-350.1 (al.)-350.1 (2001\).)-350.1 (CTCF)-350.1 (is)-350.1 (asso-)]TJ T* [(ciated)-231.4 (with)-231.4 (transcriptional)-231.4 (domain)-231.4 (boundaries)-231.4 (\(Bell)-231.4 (et)-231.4 (al.)]TJ T* [(1999\))-309 (and)-309 (can)-309 (insulate)-309 (a)-309 (promoter)-309 (from)-309 (the)-309 (influence)-309 (of)]TJ T* [(remote)-421.1 (enhancers.)-421.1 (The)-421.1 (maternally)-421.1 (derived)-421.1 (copy)-421.1 (of)-421.1 (the)]TJ /T1_1 1 Tf T* (Igf2)Tj /T1_0 1 Tf 2.0119 0 Td [(gene)-233.9 (is)-233.9 (silent)-233.9 (owing)-233.9 (to)-233.9 (the)-233.9 (binding)-233.9 (of)-233.9 (CTCF)-233.9 (between)]TJ /T1_2 1 Tf 6.9846 0 0 6.9846 428.4 755.2657 Tm [(DNA)-332.8 (methylation)-332.8 (and)-332.8 (epigenetic)-332.8 (memory)]TJ 2.6096 -101.2143 Td [(GENES)-332.8 (&)-332.8 (DEVELOPMENT)-3000 (11)]TJ ET BT /GS1 gs /T1_5 1 Tf 8 0 0 8 529.31177 806 Tm ( )Tj 0 0 1 rg /GS1 gs -16.44997 0 Td (Cold Spring Harbor Laboratory Press)Tj 0 g /GS1 gs -15.843 0 Td ( on August 22, 2022 - Published by )Tj 0 0 1 rg /GS1 gs -8.67099 0 Td (genesdev.cshlp.org)Tj 0 g /GS1 gs -8.11398 0 Td (Downloaded from )Tj ET endstream endobj 88 0 obj << /BG2 /Default /OP false /OPM 0 /SA false /SM 1 /TR2 /Default /UCR2 /Default /op false >> endobj 89 0 obj [ 90 0 R 92 0 R ] endobj 90 0 obj << /A 91 0 R /Border [ 0 0 0 ] /Rect [ 200.6 804 271.968 814 ] /Subtype /Link /Type /Annot >> endobj 91 0 obj << /S /URI /URI (http\072\057\057genesdev\056cshlp\056org\057) >> endobj 92 0 obj << /A 93 0 R /Border [ 0 0 0 ] /Rect [ 396.712 804 530.312 814 ] /Subtype /Link /Type /Annot >> endobj 93 0 obj << /S /URI /URI (http\072\057\057www\056cshlpress\056com) >> endobj 94 0 obj << /Length 11009 >> stream BT /GS0 gs /T1_0 1 Tf 8.9802 0 0 8.9802 75.5688 452.1883 Tm [(its)-354.5 (promoter)-354.5 (and)-354.5 (a)-354.5 (downstream)-354.5 (enhancer.)-354.5 (At)-354.5 (the)-354.5 (pater-)]TJ 0 -1.2222 TD [(nal)-548.6 (locus,)-548.6 (however,)-548.6 (these)-548.6 (CpG-rich)-548.6 (binding)-548.6 (sites)-548.6 (are)]TJ T* [(methylated,)-472.8 (preventing)-472.8 (CTCF)-472.8 (binding)-472.8 (and)-472.8 (thereby)-472.8 (al-)]TJ T* [(lowing)-246.8 (the)-246.8 (downstream)-246.8 (enhancer)-246.8 (to)-246.8 (activate)]TJ /T1_1 1 Tf 20.7026 0 Td (Igf2)Tj /T1_0 1 Tf 2.0248 0 Td (expres-)Tj -22.7274 -1.2222 Td [(sion.)-326.4 (Although)-326.4 (there)-326.4 (is)-326.4 (evidence)-326.4 (that)]TJ /T1_1 1 Tf 17.68 0 Td (H19)Tj /T1_0 1 Tf (/)Tj /T1_1 1 Tf (Igf2)Tj /T1_0 1 Tf 4.4383 0 Td (imprint-)Tj -22.1183 -1.2222 Td [(ing)-479.2 (involves)-479.2 (additional)-479.2 (processes)-479.2 (\(Ferguson-Smith)-479.2 (and)]TJ T* [(Surani)-494 (2001\),)-494 (the)-494 (role)-494 (of)-494 (CTCF)-494 (represents)-494 (one)-494 (of)-494 (the)]TJ T* [(clearest)-343.7 (examples)-343.7 (of)-343.7 (transcriptional)-343.7 (regulation)-343.7 (by)-343.7 (DNA)]TJ T* (methylation.)Tj 1 -1.2222 Td [(The)-284.4 (second)-284.4 (mode)-284.4 (of)-284.4 (repression)-284.4 (is)-284.4 (opposite)-284.4 (to)-284.4 (the)-284.4 (first,)]TJ -1 -1.2222 Td [(as)-352.3 (it)-352.3 (involves)-352.3 (proteins)-352.3 (that)-352.3 (are)-352.3 (attracted)-352.3 (to,)-352.3 (rather)-352.3 (than)]TJ T* [(repelled)-222.8 (by,)-222.8 (methyl-CpG)-222.8 (\(Fig.)-222.8 (1\).)-222.8 (A)-222.8 (family)-222.8 (of)-222.8 (five)-222.8 (methyl-)]TJ T* [(CpG-binding)-389.5 (proteins)-389.5 (has)-389.5 (been)-389.5 (characterized)-389.5 (that)-389.5 (each)]TJ T* [(contains)-524.6 (a)-524.6 (region)-524.6 (closely)-524.6 (related)-524.6 (to)-524.6 (the)-524.6 (methyl-CpG-)]TJ T* [(binding)-265.5 (domain)-265.5 (\(MBD\))-265.5 (of)-265.5 (MeCP2)-265.5 (\(Nan)-265.5 (et)-265.5 (al.)-265.5 (1993,)-265.5 (1997;)]TJ T* [(Cross)-277.8 (et)-277.8 (al.)-277.8 (1997;)-277.8 (Hendrich)-277.8 (and)-277.8 (Bird)-277.8 (1998\).)-277.8 (Four)-277.8 (of)-277.8 (these)]TJ T* (proteins)Tj /T1_2 1 Tf [0.1 (\227)]TJ /T1_0 1 Tf [(MBD1,)-778.4 (MBD2,)-778.4 (MBD3,)-778.4 (and)-778.4 (MeCP2)]TJ /T1_2 1 Tf [0.3 (\227)]TJ /T1_0 1 Tf (have)Tj T* [(been)-301.1 (implicated)-301.1 (in)-301.1 (methylation-dependent)-301.1 (repression)-301.1 (of)]TJ T* [(transcription)-354.8 (\(for)-354.8 (review,)-354.8 (see)-354.8 (Bird)-354.8 (and)-354.8 (Wolffe)-354.8 (1999\).)-354.8 (An)]TJ T* [(unrelated)-299.2 (protein)-299.2 (Kaiso)-299.2 (has)-299.2 (also)-299.2 (recently)-299.2 (been)-299.2 (shown)-299.2 (to)]TJ T* [(bind)-343.4 (methylated)-343.4 (DNA)-343.4 (and)-343.4 (bring)-343.4 (about)-343.4 (methylation-de-)]TJ T* [(pendent)-306.5 (repression)-306.5 (in)-306.5 (model)-306.5 (systems)-306.5 (\(Prokhortchouk)-306.5 (et)]TJ T* [(al.)-244 (2001\).)-244 (In)-244 (vitro,)-244 (Kaiso)-244 (requires)-244 (a)-244 (5)]TJ /T1_3 1 Tf [0.3 (\001)]TJ /T1_0 1 Tf 16.9537 0 Td (m)Tj 6.9846 0 0 5.4879 236.2926 214.4636 Tm (5)Tj 8.9802 0 0 8.9802 240.176 210.7219 Tm (CGm)Tj 6.9846 0 0 5.4879 263.1198 214.4636 Tm (5)Tj 8.9802 0 0 8.9802 267.0032 210.7219 Tm [(CG)-244 (motif,)]TJ -21.3175 -1.2222 Td [(and)-222.8 (binding)-222.8 (is)-222.8 (highly)-222.8 (dependent)-222.8 (on)-222.8 (the)-222.8 (presence)-222.8 (of)-222.8 (meth-)]TJ T* [(ylation.)-412.9 (The)-412.9 (presence)-412.9 (of)-412.9 (multiple)-412.9 (methyl-CpG-binding)]TJ T* [(proteins)-510.1 (with)-510.1 (repressive)-510.1 (properties)-510.1 (supports)-510.1 (the)-510.1 (argu-)]TJ T* [(ment)-563.1 (that)-563.1 (these)-563.1 (may)-563.1 (be)-563.1 (important)-563.1 (mediators)-563.1 (of)-563.1 (the)]TJ T* [(methylation)-529.3 (signal,)-529.3 (but)-529.3 (their)-529.3 (involvement)-529.3 (in)-529.3 (specific)]TJ T* [(processes)-294.5 (that)-294.5 (require)-294.5 (transduction)-294.5 (of)-294.5 (the)-294.5 (DNA)-294.5 (methyl-)]TJ T* [(ation)-364.9 (signal)-364.9 (has)-364.9 (yet)-364.9 (to)-364.9 (be)-364.9 (shown.)-364.9 (Targeted)-364.9 (mutation)-364.9 (of)]TJ T* [(the)-313.1 (gene)-313.1 (for)-313.1 (MeCP2)-313.1 (is,)-313.1 (however,)-313.1 (associated)-313.1 (with)-313.1 (neuro-)]TJ T* [(logical)-514.8 (dysfunction)-514.8 (in)-514.8 (humans)-514.8 (and)-514.8 (mice)-514.8 (\(Amir)-514.8 (et)-514.8 (al.)]TJ T* [(1999;)-257.6 (Chen)-257.6 (et)-257.6 (al.)-257.6 (2001;)-257.6 (Guy)-257.6 (et)-257.6 (al.)-257.6 (2001\),)-257.6 (and)-257.6 (mutation)-257.6 (of)]TJ T* [(the)-364.6 (mouse)]TJ /T1_1 1 Tf 5.2841 0 Td (Mbd2)Tj /T1_0 1 Tf 3.0865 0 Td [(gene)-364.6 (leads)-364.6 (to)-364.6 (a)-364.6 (maternal)-364.6 (behavior)-364.6 (de-)]TJ -8.3706 -1.2222 Td [(fect)-332.7 (\(Hendrich)-332.7 (et)-332.7 (al.)-332.7 (2001\).)]TJ /T1_4 1 Tf 28.6667 41.5 Td [(Excluding)-332.7 (DNA)-332.7 (methylation)-332.7 (by)-332.7 (denying)-277.8 (access)]TJ /T1_0 1 Tf 0 -1.8333 TD [(The)-427.1 (preceding)-427.1 (discussion)-427.1 (has)-427.1 (considered)-427.1 (some)-427.1 (mecha-)]TJ 0 -1.2222 TD [(nistic)-334 (aspects)-334 (of)-334 (de)-334 (novo)-334 (DNA)-334 (methylation)-334 (and)-334 (its)-334 (bio-)]TJ T* [(logical)-807.4 (consequences.)-807.4 (Although)-807.4 (methylation)-807.4 (affects)]TJ T* [(most)-286 (of)-286 (the)-286 (mammalian)-286 (genome,)-286 (it)-286 (is)-286 (conspicuously)-286 (ab-)]TJ T* [(sent)-514.8 (from)-514.8 (certain)-514.8 (regions.)-514.8 (Ways)-514.8 (in)-514.8 (which)-514.8 (these)-514.8 (non-)]TJ T* [(methylated)-357.9 (domains)-357.9 (may)-357.9 (arise)-357.9 (will)-357.9 (now)-357.9 (be)-357.9 (considered.)]TJ T* [(A)-389.8 (simple)-389.8 (mechanism)-389.8 (for)-389.8 (creating)-389.8 (a)-389.8 (nonmethylated)-389.8 (do-)]TJ T* [(main)-239.3 (within)-239.3 (an)-239.3 (otherwise)-239.3 (densely)-239.3 (methylated)-239.3 (genome)-239.3 (is)]TJ T* [(to)-256 (mask)-256 (a)-256 (stretch)-256 (of)-256 (DNA)-256 (by)-256 (protein)-256 (binding.)-256 (The)-256 (DNA-)]TJ T* [(binding)-344.1 (protein)-344.1 (would)-344.1 (accomplish)-344.1 (this)-344.1 (passive)-344.1 (demeth-)]TJ T* [(ylation)-537.9 (by,)-537.9 (for)-537.9 (example,)-537.9 (sterically)-537.9 (excluding)-537.9 (DNMTs)]TJ T* [(\(Bird)-355.1 (1986\).)-355.1 (The)-355.1 (feasibility)-355.1 (of)-355.1 (this)-355.1 (mechanism)-355.1 (has)-355.1 (been)]TJ T* [(verified)-492.1 (using)-492.1 (an)-492.1 (artificially)-492.1 (methylated)-492.1 (episome)-492.1 (con-)]TJ T* [(taining)-604.2 (EBNA1)-604.2 (or)-604.2 (lac)-604.2 (repressor)-604.2 (binding)-604.2 (sites)-604.2 (\(Hsieh)]TJ T* [(1999a;)-428 (Lin)-428 (et)-428 (al.)-428 (2000\).)-428 (The)-428 (idea)-428 (that)-428 (CpG)-428 (islands)-428 (are)]TJ T* [(entirely)-235.5 (attributable)-235.5 (to)-235.5 (exclusion)-235.5 (of)-235.5 (this)-235.5 (kind)-235.5 (is)-235.5 (in)-235.5 (doubt,)]TJ T* [(however,)-270.8 (as)-270.8 (in)-270.8 (vivo)-270.8 (footprinting)-270.8 (and)-270.8 (nuclease)-270.8 (accessibil-)]TJ T* [(ity)-408.1 (studies)-408.1 (show)-408.1 (CpG)-408.1 (islands)-408.1 (to)-408.1 (be)-408.1 (more)-408.1 (accessible)-408.1 (to)]TJ T* [(proteins)-429.6 (\(nucleases\))-429.6 (than)-429.6 (bulk)-429.6 (genomic)-429.6 (DNA,)-429.6 (not)-429.6 (less)]TJ T* [(\(Tazi)-394.9 (and)-394.9 (Bird)-394.9 (1990\).)-394.9 (Of)-394.9 (course,)-394.9 (it)-394.9 (is)-394.9 (possible)-394.9 (that)-394.9 (pro-)]TJ T* [(tection)-334 (is)-334 (only)-334 (present)-334 (at)-334 (the)-334 (transient)-334 (embryonic)-334 (stage)]TJ T* [(when)-365.8 (mammalian)-365.8 (de)-365.8 (novo)-365.8 (methylation)-365.8 (occurs)-365.8 (and)-365.8 (has)]TJ T* [(therefore)-263.9 (escaped)-263.9 (detection.)-263.9 (A)-263.9 (protein)-263.9 (that)-263.9 (is)-263.9 (reported)-263.9 (to)]TJ T* [(bind)-350 (unmethylated)-350.1 (CpGs)-350.1 (might)-350.1 (be)-350.1 (a)-350.1 (candidate)-350.1 (CpG-is-)]TJ T* [(land)-332.7 (protector)-332.7 (\(Voo)-332.7 (et)-332.7 (al.)-332.7 (2000\).)]TJ /T1_4 1 Tf 0 -3.5833 TD [(Immunity)-332.7 (to)-332.7 (DNA)-332.7 (methylation)-332.7 (caused)]TJ 0 -1.2222 TD [(by)-332.7 (transcriptionally)-332.7 (active)-332.7 (chromatin:)]TJ T* [(the)-332.7 (origin)-332.7 (of)-332.7 (unmethylated)-332.7 (CpG)-277.8 (islands)]TJ /T1_0 1 Tf 0 -1.8333 TD [(Many)-396.8 (of)-396.8 (the)-396.8 (known)-396.8 (biological)-396.8 (effects)-396.8 (of)-396.8 (DNA)-396.8 (methyl-)]TJ 0 -1.2222 TD [(ation)-241.5 (are)-241.5 (associated)-241.5 (with)-241.5 (CpG)-241.5 (islands.)-241.5 (It)-241.5 (has)-241.5 (been)-241.5 (argued)]TJ T* [(above)-236.7 (that)-236.7 (their)-236.7 (methylation)-236.7 (in)-236.7 (the)-236.7 (early)-236.7 (embryo)-236.7 (follows)]TJ ET q /GS1 gs 324 0 0 239.22 242.4841 494.0957 cm 1.2222 TL /Im0 Do Q BT /T1_4 1 Tf 7.9824 0 0 7.9824 75.5688 703.6327 Tm [(Figure)-391 (1.)]TJ /T1_0 1 Tf 5.114 0 Td [(Mechanisms)-391 (of)-391 (transcriptional)]TJ -5.114 -1.25 Td [(repression)-234 (by)-234 (DNA)-234 (methylation.)-234 (A)-234 (stretch)]TJ 0 -1.25 TD [(of)-510.7 (nucleosomal)-510.7 (DNA)-510.7 (is)-510.7 (shown)-510.7 (with)-510.7 (all)]TJ T* [(CpGs)-400.6 (methylated)-400.6 (\(red)-400.6 (circles\).)-400.6 (Below)-400.6 (the)]TJ T* [(diagram)-231.2 (is)-231.2 (a)-231.2 (transcription)-231.2 (factor)-231.2 (that)-231.2 (is)-231.2 (un-)]TJ T* [(able)-492.9 (to)-492.9 (bind)-492.9 (its)-492.9 (recognition)-492.9 (site)-492.9 (when)-492.9 (a)]TJ T* [(methylated)-380.7 (CpG)-380.7 (is)-380.7 (within)-380.7 (it.)-380.7 (Many)-380.7 (tran-)]TJ T* [(scription)-489.7 (factors)-489.7 (are)-489.7 (repelled)-489.7 (by)-489.7 (methyl-)]TJ T* [(ation,)-709.5 (including)-709.5 (the)-709.5 (boundary)-709.5 (element)]TJ T* [(protein)-230.1 (CTCF)-230.1 (\(see)-230.1 (text\).)-230.1 (Above)-230.1 (the)-230.1 (line)-230.1 (are)]TJ T* [(protein)-250 (complexes)-250 (that)-250 (can)-250 (be)-250 (attracted)-250 (by)]TJ T* [(methylation,)-483.7 (including)-483.7 (the)-483.7 (methyl-CpG-)]TJ T* [(binding)-533.7 (protein)-533.7 (MeCP2)-533.7 (\(plus)-533.7 (the)-533.7 (Sin3A)]TJ T* [(histone)-333.8 (deacetylase)-333.8 (complex\),)-333.8 (the)-333.8 (MeCP1)]TJ T* [(complex)-987.2 (comprising)-987.2 (MBD2)-987.2 (plus)-987.2 (the)]TJ T* [(NuRD)-456.3 (corepressor)-456.3 (complex,)-456.3 (and)-456.3 (the)-456.3 (un-)]TJ T* [(characterized)-236.9 (MBD1)-236.9 (and)-236.9 (Kaiso)-236.9 (complexes.)]TJ T* [(MeCP2)-917.3 (and)-917.3 (MBD1)-917.3 (are)-917.3 (chromosome-)]TJ T* [(bound)-456 (proteins,)-456 (whereas)-456 (MeCP1)-456 (may)-456 (be)]TJ T* [(less)-318.2 (tightly)-318.2 (bound.)-318.2 (Kaiso)-318.2 (has)-318.2 (not)-318.2 (yet)-318.2 (been)]TJ T* [(shown)-356.9 (to)-356.9 (associate)-356.9 (with)-356.9 (methylated)-356.9 (sites)]TJ T* [(in)-332.7 (vivo.)]TJ /T1_4 1 Tf 6.9846 0 0 6.9846 75.5688 755.2657 Tm (Bird)Tj 0 -101.2143 TD [(12)-3000 (GENES)-332.8 (&)-332.8 (DEVELOPMENT)]TJ ET BT /GS2 gs /T1_5 1 Tf 8 0 0 8 529.31177 806 Tm ( )Tj 0 0 1 rg /GS2 gs -16.44997 0 Td (Cold Spring Harbor Laboratory Press)Tj 0 g /GS2 gs -15.843 0 Td ( on August 22, 2022 - Published by )Tj 0 0 1 rg /GS2 gs -8.67099 0 Td (genesdev.cshlp.org)Tj 0 g /GS2 gs -8.11398 0 Td (Downloaded from )Tj ET endstream endobj 95 0 obj << /BG2 /Default /HT2 /Default /OP false /OPM 1 /SA false /SM 0.02 /TR2 /Default /Type /ExtGState /UCR2 /Default /op false >> endobj 96 0 obj << /BG2 /Default /OP false /OPM 0 /SA false /SM 1 /TR2 /Default /UCR2 /Default /op false >> endobj 97 0 obj << /BitsPerComponent 8 /ColorSpace /DeviceCMYK /Filter /DCTDecode /Height 478 /Name /X /Subtype /Image /Type /XObject /Width 648 /Length 85021 >> stream AdobedC     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(repressors)-699.9 (that)-699.9 (exhibit)]TJ T* [(unique)-449.9 (localization)-449.9 (properties)-449.9 (to)-449.9 (heterochromatin.)]TJ /T1_2 1 Tf 24.529 0 Td [(J.)-449.9 (Biol.)]TJ -24.529 -1.25 Td (Chem.)Tj /T1_3 1 Tf 3.4438 0 Td (276:)Tj /T1_0 1 Tf 2.2241 0 Td (32282)Tj /T1_4 1 Tf (\226)Tj /T1_0 1 Tf (32287.)Tj -7.1679 -1.25 Td [(Bannister,)-226.2 (A.J.,)-226.2 (Zegerman,)-226.2 (P.,)-226.2 (Partridge,)-226.2 (J.F.,)-226.2 (Miska,)-226.2 (E.A.,)-226.2 (Thom-)]TJ 1.5 -1.25 Td [(as,)-434.3 (J.O.,)-434.3 (Allshire,)-434.3 (R.C.,)-434.3 (and)-434.3 (Kouzarides,)-434.3 (T.)-434.3 (2001.)-434.3 (Selective)]TJ T* [(recognition)-236.9 (of)-236.9 (methylated)-236.9 (lysine)-236.9 (9)-236.9 (on)-236.9 (histone)-236.9 (H3)-236.9 (by)-236.9 (the)-236.9 (HP1)]TJ T* [(chromo)-332.7 (domain.)]TJ /T1_2 1 Tf 7.9996 0 Td (Nature)Tj /T1_3 1 Tf 3.6108 0 Td (410:)Tj /T1_0 1 Tf 2.2241 0 Td (120)Tj /T1_4 1 Tf (\226)Tj /T1_0 1 Tf (124.)Tj -15.3345 -1.25 Td [(Baylin,)-323.5 (S.B.)-323.5 (and)-323.5 (Herman,)-323.5 (J.G.)-323.5 (2000.)-323.5 (DNA)-323.5 (hypermethylation)-323.5 (in)]TJ 1.5 -1.25 Td [(tumorigenesis:)-607.2 (Epigenetics)-607.2 (joins)-607.3 (genetics.)]TJ /T1_2 1 Tf 20.8153 0 Td [(Trends)-607.3 (Genet.)]TJ /T1_3 1 Tf -20.8153 -1.25 Td (16:)Tj /T1_0 1 Tf 1.6681 0 Td (168)Tj /T1_4 1 Tf (\226)Tj /T1_0 1 Tf (174.)Tj -3.1681 -1.25 Td [(Beard,)-475.1 (C.,)-475.1 (Li,)-475.1 (E.,)-475.1 (and)-475.2 (Jaenisch,)-475.1 (R.)-475.2 (1995.)-475.1 (Loss)-475.2 (of)-475.2 (methylation)]TJ 1.5 -1.25 Td [(activates)-318.9 (Xist)-318.9 (in)-318.9 (somatic)-318.9 (but)-318.9 (not)-318.9 (in)-318.9 (embryonic)-318.9 (cells.)]TJ /T1_2 1 Tf 24.8684 0 Td (Genes)Tj /T1_0 1 Tf -24.8684 -1.25 Td (&)Tj /T1_2 1 Tf 1.2218 0 Td (Dev.)Tj /T1_3 1 Tf 2.4998 0 Td (9:)Tj /T1_0 1 Tf 1.1121 0 Td (2325)Tj /T1_4 1 Tf (\226)Tj /T1_0 1 Tf (2334.)Tj -6.3336 -1.25 Td [(Bell,)-349.1 (A.C.)-349.1 (and)-349.1 (Felsenfeld,)-349.1 (G.)-349.1 (2000.)-349.1 (Methylation)-349.1 (of)-349.1 (a)-349.1 (CTCF-de-)]TJ 1.5 -1.25 Td [(pendent)-330.3 (boundary)-330.3 (controls)-330.3 (imprinted)-330.3 (expression)-330.3 (of)-330.3 (the)-330.3 (Igf2)]TJ T* (gene.)Tj /T1_2 1 Tf 2.7218 0 Td (Nature)Tj /T1_3 1 Tf 3.6108 0 Td (405:)Tj /T1_0 1 Tf 2.2241 0 Td (482)Tj /T1_4 1 Tf (\226)Tj /T1_0 1 Tf (485.)Tj -10.0567 -1.25 Td [(Bell,)-484.7 (A.C.,)-484.7 (West,)-484.7 (A.G.,)-484.7 (and)-484.7 (Felsenfeld,)-484.7 (G.)-484.7 (1999.)-484.7 (The)-484.7 (protein)]TJ 1.5 -1.25 Td [(CTCF)-343 (is)-343 (required)-343.1 (for)-343 (the)-343 (enhancer)-343 (blocking)-343 (activity)-343.1 (of)-343 (ver-)]TJ T* [(tebrate)-332.7 (insulators.)]TJ /T1_2 1 Tf 8.7766 0 Td (Cell)Tj /T1_3 1 Tf 2.2768 0 Td (98:)Tj /T1_0 1 Tf 1.6681 0 Td (387)Tj /T1_4 1 Tf (\226)Tj /T1_0 1 Tf (396.)Tj -14.2215 -1.25 Td [(Bender,)-242.2 (J.)-242.2 (2001.)-242.2 (A)-242.2 (vicious)-242.2 (cycle.)-242.2 (RNA)-242.2 (silencing)-242.2 (and)-242.2 (DNA)-242.2 (meth-)]TJ 1.5 -1.25 Td [(ylation)-332.8 (in)-332.8 (plants.)]TJ /T1_2 1 Tf 8.3313 0 Td (Cell)Tj /T1_3 1 Tf 2.2768 0 Td (106:)Tj /T1_0 1 Tf 2.2241 0 Td (129)Tj /T1_4 1 Tf (\226)Tj /T1_0 1 Tf (132.)Tj -14.3322 -1.25 Td [(Bestor,)-552.6 (T.H.)-552.6 (1992.)-552.6 (Activation)-552.6 (of)-552.6 (mammalian)-552.6 (DNA)-552.6 (methyl-)]TJ 1.5 -1.25 Td [(transferase)-379.3 (by)-379.3 (cleavage)-379.3 (of)-379.3 (a)-379.3 (Zn)-379.3 (binding)-379.3 (regulatory)-379.3 (domain.)]TJ /T1_2 1 Tf T* [(EMBO)-332.8 (J.)]TJ /T1_3 1 Tf 4.3875 0 Td (11:)Tj /T1_0 1 Tf 1.6681 0 Td (2611)Tj /T1_4 1 Tf (\226)Tj /T1_0 1 Tf (2617.)Tj /T1_4 1 Tf -7.5557 -1.25 Td (\227\227\227)Tj /T1_0 1 Tf [(.)-274.9 (2000.)-274.9 (The)-274.9 (DNA)-274.9 (methyltransferases)-274.9 (of)-274.9 (mammals.)]TJ /T1_2 1 Tf 26.5893 0 Td (Hum.)Tj -25.0894 -1.25 Td [(Mol.)-332.7 (Genet.)]TJ /T1_3 1 Tf 5.8876 0 Td (9:)Tj /T1_0 1 Tf 1.1121 0 Td (2395)Tj /T1_4 1 Tf (\226)Tj /T1_0 1 Tf (2402.)Tj -8.4997 -1.25 Td [(Bestor,)-244.3 (T.)-244.3 (and)-244.3 (Tycko,)-244.3 (B.)-244.3 (1996.)-244.3 (Creation)-244.3 (of)-244.3 (genomic)-244.3 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<< /Length 21075 >> stream BT /GS0 gs /T1_0 1 Tf 7.9824 0 0 7.9824 87.5424 727.3275 Tm (patterns.)Tj /T1_1 1 Tf 4.3888 0 Td [(Nat.)-332.7 (Genet.)]TJ /T1_2 1 Tf 5.8326 0 Td (12:)Tj /T1_0 1 Tf 1.6681 0 Td (363)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (367.)Tj -13.3895 -1.25 Td [(Bhattacharya,)-302.2 (S.K.,)-302.2 (Ramchandani,)-302.2 (S.,)-302.2 (Cervoni,)-302.2 (N.,)-302.2 (and)-302.2 (Szyf,)-302.2 (M.)]TJ 1.5 -1.25 Td [(1999.)-386 (A)-386 (mammalian)-386 (protein)-386 (with)-386 (specific)-386 (demethylase)-386 (ac-)]TJ 0 -1.25 TD [(tivity)-332.8 (for)-332.7 (mCpG)-332.8 (DNA.)]TJ /T1_1 1 Tf 11.0541 0 Td (Nature)Tj /T1_2 1 Tf 3.6108 0 Td (397:)Tj /T1_0 1 Tf 2.2241 0 Td (579)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (583.)Tj -18.389 -1.25 Td [(Birchler,)-305.8 (J.A.,)-305.8 (Bhadra,)-305.8 (M.P.,)-305.8 (and)-305.8 (Bhadra,)-305.8 (U.)-305.8 (2000.)-305.8 (Making)-305.8 (noise)]TJ 1.5 -1.25 Td [(about)-240.4 (silence:)-240.4 (Repression)-240.4 (of)-240.4 (repeated)-240.4 (genes)-240.4 (in)-240.4 (animals.)]TJ /T1_1 1 Tf 25.3106 0 Td (Curr.)Tj -25.3106 -1.25 Td [(Opin.)-332.7 (Genet.)-332.7 (Dev.)]TJ /T1_2 1 Tf 8.9433 0 Td (10:)Tj /T1_0 1 Tf 1.6681 0 Td (211)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (216.)Tj -12.1115 -1.25 Td [(Bird,)-509.9 (A.P.)-509.9 (1986.)-509.9 (CpG-rich)-510 (islands)-510 (and)-510 (the)-509.9 (function)-510 (of)-509.9 (DNA)]TJ 1.5 -1.25 Td (methylation.)Tj /T1_1 1 Tf 6.3328 0 Td (Nature)Tj /T1_2 1 Tf 3.6108 0 Td (321:)Tj /T1_0 1 Tf 2.2241 0 Td (209)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (213.)Tj /T1_3 1 Tf -13.6677 -1.25 Td (\227\227\227)Tj /T1_0 1 Tf [(.)-460.2 (1987.)-460.2 (CpG)-460.2 (islands)-460.2 (as)-460.2 (gene)-460.2 (markers)-460.2 (in)-460.2 (the)-460.2 (vertebrate)]TJ 1.5 -1.25 Td (nucleus.)Tj /T1_1 1 Tf 4.2208 0 Td [(Trends)-332.8 (Genet.)]TJ /T1_2 1 Tf 6.9986 0 Td (3:)Tj /T1_0 1 Tf 1.1121 0 Td (342)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (347.)Tj /T1_3 1 Tf -13.8315 -1.25 Td (\227\227\227)Tj /T1_0 1 Tf [(.)-583.8 (1995.)-583.8 (Gene)-583.8 (number,)-583.8 (noise)-583.8 (reduction)-583.8 (and)-583.8 (biological)]TJ 1.5 -1.25 Td (complexity.)Tj /T1_1 1 Tf 5.8338 0 Td [(Trends)-332.8 (Genet.)]TJ /T1_2 1 Tf 6.9986 0 Td (11:)Tj /T1_0 1 Tf 1.6681 0 Td (94)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (100.)Tj /T1_3 1 Tf -16.0005 -1.25 Td (\227\227\227)Tj /T1_0 1 Tf [(.)-369.7 (1997.)-369.7 (Does)-369.7 (DNA)-369.7 (methylation)-369.7 (control)-369.7 (transposition)-369.7 (of)]TJ 1.5 -1.25 Td [(selfish)-227.3 (elements)-227.3 (in)-227.3 (the)-227.3 (germline.)]TJ /T1_1 1 Tf 15.1876 0 Td [(Trends)-227.3 (Genet.)]TJ /T1_2 1 Tf 6.7876 0 Td (13:)Tj /T1_0 1 Tf 1.6681 0 Td (469)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (470.)Tj -25.1433 -1.25 Td [(Bird,)-528.1 (A.)-528.1 (and)-528.1 (Wolffe,)-528.1 (A.P.)-528.1 (1999.)-528.1 (Methylation-induced)-528.1 (repres-)]TJ 1.5 -1.25 Td (sion)Tj /T1_3 1 Tf (\227)Tj /T1_0 1 Tf [(Belts,)-332.7 (braces)-332.7 (and)-332.8 (chromatin.)]TJ /T1_1 1 Tf 16.4972 0 Td (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (99:)Tj /T1_0 1 Tf 1.6681 0 Td (451)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (454.)Tj -21.9421 -1.25 Td [(Bird,)-243.6 (A.P.,)-243.6 (Taggart,)-243.6 (M.H.,)-243.6 (and)-243.6 (Smith,)-243.6 (B.A.)-243.6 (1979.)-243.6 (Methylated)-243.6 (and)]TJ 1.5 -1.25 Td [(unmethylated)-536.6 (DNA)-536.6 (compartments)-536.6 (in)-536.6 (the)-536.6 (sea)-536.6 (urchin)-536.6 (ge-)]TJ T* (nome.)Tj /T1_1 1 Tf 3.2218 0 Td (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (17:)Tj /T1_0 1 Tf 1.6681 0 Td (889)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (901.)Tj -8.6667 -1.25 Td [(Bird,)-287.3 (A.P.,)-287.3 (Taggart,)-287.3 (M.H.,)-287.3 (Nicholls,)-287.3 (R.D.,)-287.3 (and)-287.3 (Higgs,)-287.3 (D.R.)-287.3 (1987.)]TJ 1.5 -1.25 Td [(Non-methylated)-259.2 (CpG-rich)-259.2 (islands)-259.2 (at)-259.2 (the)-259.2 (human)]TJ /T1_4 1 Tf 22.4427 0 Td (\001)Tj /T1_0 1 Tf [(-globin)-259.2 (lo-)]TJ -22.4427 -1.25 Td [(cus:)-362.2 (Implications)-362.2 (for)-362.2 (evolution)-362.2 (of)-362.2 (the)]TJ /T1_4 1 Tf 17.9505 0 Td (\001)Tj /T1_0 1 Tf [(-globin)-362.2 (pseudogene.)]TJ /T1_1 1 Tf -17.9505 -1.25 Td [(EMBO)-332.8 (J.)]TJ /T1_2 1 Tf 4.3875 0 Td (6:)Tj /T1_0 1 Tf 1.1121 0 Td (999)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1004.)Tj -6.9996 -1.25 Td [(Birger,)-250.4 (Y.,)-250.4 (Shemer,)-250.4 (R.,)-250.4 (Perk,)-250.4 (J.,)-250.4 (and)-250.4 (Razin,)-250.4 (A.)-250.4 (1999.)-250.4 (The)-250.4 (imprint-)]TJ 1.5 -1.25 Td [(ing)-332.8 (box)-332.8 (of)-332.7 (the)-332.7 (mouse)-332.7 (Igf2r)-332.7 (gene.)]TJ /T1_1 1 Tf 15.3854 0 Td (Nature)Tj /T1_2 1 Tf 3.6108 0 Td (397:)Tj /T1_0 1 Tf 2.2241 0 Td (84)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (88.)Tj -22.7203 -1.25 Td (Bourc)Tj /T1_3 1 Tf (\222)Tj /T1_0 1 Tf [(his,)-392.4 (D.,)-392.4 (Le)-392.4 (Bourhis,)-392.4 (D.,)-392.4 (Patin,)-392.4 (D.,)-392.4 (Niveleau,)-392.4 (A.,)-392.4 (Comiz-)]TJ 1.5 -1.25 Td [(zoli,)-378.9 (P.,)-378.9 (Renard,)-378.9 (J.,)-378.9 (and)-378.9 (Viegas-Pequignot,)-378.9 (E.)-378.9 (2001.)-378.9 (Delayed)]TJ T* [(and)-229.1 (incomplete)-229.1 (reprogramming)-229.1 (of)-229.1 (chromosome)-229.1 (methylation)]TJ T* [(patterns)-1338.4 (in)-1338.4 (bovine)-1338.4 (cloned)-1338.4 (embryos.)]TJ /T1_1 1 Tf 21.8053 0 Td [(Curr.)-1338.4 (Biol.)]TJ /T1_2 1 Tf -21.8053 -1.25 Td (11:)Tj /T1_0 1 Tf 1.6681 0 Td (1542)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1546.)Tj -3.1681 -1.25 Td [(Boyes,)-310.7 (J.)-310.7 (and)-310.7 (Bird,)-310.7 (A.)-310.7 (1992.)-310.7 (Repression)-310.7 (of)-310.7 (genes)-310.7 (by)-310.7 (DNA)-310.7 (meth-)]TJ 1.5 -1.25 Td [(ylation)-267.8 (depends)-267.8 (on)-267.8 (CpG)-267.8 (density)-267.8 (and)-267.8 (promoter)-267.8 (strength:)-267.8 (Evi-)]TJ T* [(dence)-512.8 (for)-512.8 (involvement)-512.8 (of)-512.8 (a)-512.8 (methyl-CpG)-512.8 (binding)-512.8 (protein.)]TJ /T1_1 1 Tf T* [(EMBO)-332.8 (J.)]TJ /T1_2 1 Tf 4.3875 0 Td (11:)Tj /T1_0 1 Tf 1.6681 0 Td (327)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (333.)Tj -7.5556 -1.25 Td [(Brandeis,)-225.5 (M.,)-225.5 (Frank,)-225.5 (D.,)-225.5 (Keshet,)-225.5 (I.,)-225.5 (Siegried,)-225.5 (Z.,)-225.5 (Mendelsohn,)-225.5 (M.,)]TJ 1.5 -1.25 Td [(Nemes,)-347 (A.,)-347 (Temper,)-347 (V.,)-347 (Razin,)-347 (A.,)-346.9 (and)-347 (Cedar,)-347 (H.)-347 (1994.)-347 (Sp1)]TJ T* [(elements)-407 (protect)-407 (a)-407 (CpG)-407 (island)-407 (from)-407 (de)-407 (novo)-407 (methylation.)]TJ /T1_1 1 Tf T* (Nature)Tj /T1_2 1 Tf 3.6108 0 Td (371:)Tj /T1_0 1 Tf 2.2241 0 Td (435)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (438.)Tj -7.3349 -1.25 Td [(Cavalli,)-404.8 (G.)-404.8 (and)-404.8 (Paro,)-404.8 (R.)-404.8 (1998.)-404.8 (The)]TJ /T1_1 1 Tf 16.892 0 Td (Drosophila)Tj /T1_0 1 Tf 5.5719 0 Td [(Fab-7)-404.8 (chromo-)]TJ -20.9639 -1.25 Td [(somal)-321 (element)-321 (conveys)-321 (epigenetic)-321 (inheritance)-321 (during)-321 (mito-)]TJ T* [(sis)-332.8 (and)-332.8 (meiosis.)]TJ /T1_1 1 Tf 7.7183 0 Td (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (93:)Tj /T1_0 1 Tf 1.6681 0 Td (505)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (518.)Tj /T1_3 1 Tf -13.1632 -1.25 Td (\227\227\227)Tj /T1_0 1 Tf [(.)-393.5 (1999.)-393.5 (Epigenetic)-393.5 (inheritance)-393.5 (of)-393.5 (active)-393.5 (chromatin)-393.5 (after)]TJ 1.5 -1.25 Td [(removal)-332.7 (of)-332.7 (the)-332.8 (main)-332.8 (transactivator.)]TJ /T1_1 1 Tf 16.9419 0 Td (Science)Tj /T1_2 1 Tf 3.8328 0 Td (286:)Tj /T1_0 1 Tf 2.2241 0 Td (955)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (958.)Tj -24.4989 -1.25 Td [(Chan,)-385.7 (M.F.,)-385.7 (van)-385.7 (Amerongen,)-385.7 (R.,)-385.7 (Nijjar,)-385.7 (T.,)-385.7 (Cuppen,)-385.7 (E.,)-385.7 (Jones,)]TJ 1.5 -1.25 Td [(P.A.,)-319.6 (and)-319.6 (Laird,)-319.6 (P.W.)-319.6 (2001.)-319.6 (Reduced)-319.6 (rates)-319.6 (of)-319.6 (gene)-319.6 (loss,)-319.6 (gene)]TJ T* [(silencing,)-311.8 (and)-311.8 (gene)-311.8 (mutation)-311.8 (in)-311.8 (dnmt1-deficient)-311.8 (embryonic)]TJ T* [(stem)-332.8 (cells.)]TJ /T1_1 1 Tf 5.3306 0 Td [(Mol.)-332.7 (Cell.)-332.7 (Biol.)]TJ /T1_2 1 Tf 7.4983 0 Td (21:)Tj /T1_0 1 Tf 1.6681 0 Td (7587)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (7600.)Tj -15.997 -1.25 Td [(Chen,)-392.8 (R.Z.,)-392.8 (Pettersson,)-392.8 (U.,)-392.8 (Beard,)-392.8 (C.,)-392.8 (Jackson-Grusby,)-392.8 (L.,)-392.8 (and)]TJ 1.5 -1.25 Td [(Jaenisch,)-361.5 (R.)-361.5 (1998.)-361.5 (DNA)-361.5 (hypomethylation)-361.5 (leads)-361.5 (to)-361.5 (elevated)]TJ T* [(mutation)-332.8 (rates.)]TJ /T1_1 1 Tf 7.4986 0 Td (Nature)Tj /T1_2 1 Tf 3.6108 0 Td (395:)Tj /T1_0 1 Tf 2.2241 0 Td (89)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (93.)Tj -14.8335 -1.25 Td [(Chen,)-291.9 (R.Z.,)-291.9 (Akbarian,)-291.9 (S.,)-291.9 (Tudor,)-291.9 (M.,)-291.9 (and)-291.9 (Jaenisch,)-291.9 (R.)-291.9 (2001.)-291.9 (De-)]TJ 1.5 -1.25 Td [(ficiency)-393.8 (of)-393.8 (methyl-CpG)-393.8 (binding)-393.8 (protein-2)-393.8 (in)-393.8 (CNS)-393.8 (neurons)]TJ T* [(results)-698.9 (in)-698.9 (a)-698.9 (Rett-like)-698.9 (phenotype)-698.9 (in)-698.9 (mice.)]TJ /T1_1 1 Tf 21.8903 0 Td [(Nat.)-698.9 (Genet.)]TJ /T1_2 1 Tf -21.8903 -1.25 Td (27:)Tj /T1_0 1 Tf 1.6681 0 Td (327)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (331.)Tj -3.1681 -1.25 Td [(Chu,)-580.3 (W.M.,)-580.3 (Ballard,)-580.3 (R.,)-580.3 (Carpick,)-580.3 (B.W.,)-580.3 (Williams,)-580.3 (B.R.,)-580.3 (and)]TJ 1.5 -1.25 Td [(Schmid,)-433.2 (C.W.)-433.2 (1998.)-433.2 (Potential)-433.2 (Alu)-433.2 (function:)-433.2 (Regulation)-433.2 (of)]TJ T* [(the)-357.6 (activity)-357.6 (of)-357.6 (double-stranded)-357.6 (RNA-activated)-357.6 (kinase)-357.6 (PKR.)]TJ /T1_1 1 Tf T* [(Mol.)-332.7 (Cell.)-332.7 (Biol.)]TJ /T1_2 1 Tf 7.4983 0 Td (18:)Tj /T1_0 1 Tf 1.6681 0 Td (58)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (68.)Tj -10.6664 -1.25 Td [(Cogoni,)-456.7 (C.,)-456.7 (Irelan,)-456.7 (J.T.,)-456.7 (Schumacher,)-456.7 (M.,)-456.7 (Schmidhauser,)-456.7 (T.J.,)]TJ 1.5 -1.25 Td [(Selker,)-427.6 (E.U.,)-427.6 (and)-427.6 (Macino,)-427.6 (G.)-427.6 (1996.)-427.6 (Transgene)-427.6 (silencing)-427.6 (of)]TJ T* [(the)-220.2 (al-1)-220.2 (gene)-220.2 (in)-220.2 (vegetative)-220.2 (cells)-220.2 (of)]TJ /T1_1 1 Tf 15.5404 0 Td (Neurospora)Tj /T1_0 1 Tf 5.6103 0 Td [(is)-220.2 (mediated)-220.2 (by)]TJ -21.1507 -1.25 Td [(a)-365.1 (cytoplasmic)-365.1 (effector)-365.1 (and)-365.1 (does)-365.1 (not)-365.1 (depend)-365.1 (on)-365.1 (DNA)]TJ /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (DNA)Tj T* [(interactions)-332.7 (or)-332.7 (DNA)-332.8 (methylation.)]TJ /T1_1 1 Tf 16.3312 0 Td [(EMBO)-332.8 (J.)]TJ /T1_2 1 Tf 4.3875 0 Td (15:)Tj /T1_0 1 Tf 1.6681 0 Td (3153)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (3163.)Tj -23.8869 -1.25 Td [(Colot,)-462.4 (V.)-462.4 (and)-462.4 (Rossignol,)-462.4 (J.L.)-462.4 (1999.)-462.4 (Eukaryotic)-462.4 (DNA)-462.4 (methyl-)]TJ 1.5 -1.25 Td [(ation)-332.8 (as)-332.7 (an)-332.8 (evolutionary)-332.8 (device.)]TJ /T1_1 1 Tf 15.2209 0 Td (BioEssays)Tj /T1_2 1 Tf 4.9438 0 Td (21:)Tj /T1_0 1 Tf 1.6681 0 Td (402)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (411.)Tj 8.9172 81.25 Td [(Colot,)-268.1 (V.,)-268.1 (Maloisel,)-268.1 (I.L.,)-268.1 (and)-268.1 (Rossignol,)-268.1 (J.-L.)-268.1 (1996.)-268.1 (Interchromo-)]TJ 1.5 -1.25 Td [(somal)-289.4 (transfer)-289.4 (of)-289.4 (epigenetic)-289.4 (states)-289.4 (in)]TJ /T1_1 1 Tf 17.2897 0 Td (Ascobolus)Tj /T1_0 1 Tf [-0.1 (:)-289.4 (Transfer)-289.4 (of)]TJ -17.2897 -1.25 Td [(DNA)-265.3 (methylation)-265.3 (is)-265.3 (mechanistically)-265.3 (related)-265.3 (to)-265.3 (homologous)]TJ T* (recombination.)Tj /T1_1 1 Tf 7.3888 0 Td (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (86:)Tj /T1_0 1 Tf 1.6681 0 Td (855)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (864.)Tj -12.8337 -1.25 Td [(Cosma,)-398.1 (M.P.,)-398.1 (Tanaka,)-398.1 (T.,)-398.1 (and)-398.1 (Nasmyth,)-398.1 (K.)-398.1 (1999.)-398.1 (Ordered)-398.1 (re-)]TJ 1.5 -1.25 Td [(cruitment)-228.3 (of)-228.3 (transcription)-228.3 (and)-228.3 (chromatin)-228.3 (remodeling)-228.4 (factors)]TJ T* [(to)-560.7 (a)-560.7 (cell)-560.7 (cycle-)-560.7 (and)-560.7 (developmentally-regulated)-560.7 (promoter.)]TJ /T1_1 1 Tf T* (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (97:)Tj /T1_0 1 Tf 1.6681 0 Td (299)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (311.)Tj -5.4449 -1.25 Td [(Costello,)-361.5 (J.F.)-361.5 (and)-361.5 (Plass,)-361.5 (C.)-361.5 (2001.)-361.5 (Methylation)-361.5 (matters.)]TJ /T1_1 1 Tf 25.9504 0 Td [(J.)-361.5 (Med.)]TJ -24.4504 -1.25 Td (Genet.)Tj /T1_2 1 Tf 3.4438 0 Td (38:)Tj /T1_0 1 Tf 1.6681 0 Td (285)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (303.)Tj -6.6119 -1.25 Td [(Cross,)-345.9 (S.H.,)-345.9 (Meehan,)-345.9 (R.R.,)-345.9 (Nan,)-345.9 (X.,)-345.9 (and)-345.9 (Bird,)-345.9 (A.)-345.9 (1997.)-345.9 (A)-345.9 (com-)]TJ 1.5 -1.25 Td [(ponent)-351.2 (of)-351.2 (the)-351.2 (transcriptional)-351.2 (repressor)-351.2 (MeCP1)-351.2 (is)-351.2 (related)-351.2 (to)]TJ T* [(mammalian)-318.6 (DNA)-318.5 (methyltransferase)-318.5 (and)-318.5 (trithorax-like)-318.5 (pro-)]TJ T* (tein.)Tj /T1_1 1 Tf 2.4438 0 Td [(Nat.)-332.7 (Genet.)]TJ /T1_2 1 Tf 5.8326 0 Td (16:)Tj /T1_0 1 Tf 1.6681 0 Td (256)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (259.)Tj -11.4444 -1.25 Td [(Cuadrado,)-385.3 (M.,)-385.3 (Sacristan,)-385.3 (M.,)-385.3 (and)-385.3 (Antequera,)-385.3 (F.)-385.3 (2001.)-385.3 (Species-)]TJ 1.5 -1.25 Td [(specific)-409.8 (organization)-409.8 (of)-409.8 (CpG)-409.8 (island)-409.8 (promoters)-409.8 (at)-409.8 (mamma-)]TJ T* [(lian)-332.7 (homologous)-332.7 (genes.)]TJ /T1_1 1 Tf 11.2754 0 Td [(EMBO)-332.8 (Rep.)]TJ /T1_2 1 Tf 5.8326 0 Td (2:)Tj /T1_0 1 Tf 1.1121 0 Td (586)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (592.)Tj -19.72 -1.25 Td [(Daniels,)-392 (R.,)-392 (Lowell,)-392.1 (S.,)-392 (Bolton,)-392.1 (V.,)-392 (and)-392 (Monk,)-392 (M.)-392.1 (1997.)-392.1 (Tran-)]TJ 1.5 -1.25 Td [(scription)-321.4 (of)-321.4 (tissue-specific)-321.4 (genes)-321.4 (in)-321.4 (human)-321.4 (preimplantation)]TJ T* (embryos.)Tj /T1_1 1 Tf 4.5558 0 Td [(Hum.)-332.7 (Reprod.)]TJ /T1_2 1 Tf 6.9436 0 Td (12:)Tj /T1_0 1 Tf 1.6681 0 Td (2251)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2256.)Tj -14.6675 -1.25 Td [(Delgado,)-369.3 (S.,)-369.3 (Gomez,)-369.3 (M.,)-369.3 (Bird,)-369.3 (A.,)-369.3 (and)-369.3 (Antequera,)-369.3 (F.)-369.3 (1998.)-369.3 (Ini-)]TJ 1.5 -1.25 Td [(tiation)-428.3 (of)-428.3 (DNA)-428.3 (replication)-428.3 (at)-428.3 (CpG)-428.3 (islands)-428.3 (in)-428.3 (mammalian)]TJ T* (chromosomes.)Tj /T1_1 1 Tf 7.0548 0 Td [(EMBO)-332.8 (J.)]TJ /T1_2 1 Tf 4.3875 0 Td (17:)Tj /T1_0 1 Tf 1.6681 0 Td (2426)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2435.)Tj -14.6105 -1.25 Td [(Dennis,)-300.8 (K.,)-300.8 (Fan,)-300.8 (T.,)-300.8 (Geiman,)-300.8 (T.,)-300.8 (Yan,)-300.8 (Q.,)-300.8 (and)-300.8 (Muegge,)-300.8 (K.)-300.8 (2001.)]TJ 1.5 -1.25 Td [(Lsh,)-342.3 (a)-342.3 (member)-342.3 (of)-342.3 (the)-342.3 (SNF2)-342.3 (family,)-342.3 (is)-342.3 (required)-342.3 (for)-342.3 (genome-)]TJ T* [(wide)-332.7 (methylation.)]TJ /T1_1 1 Tf 8.8876 0 Td (Genes)Tj /T1_0 1 Tf 3.2208 0 Td (&)Tj /T1_1 1 Tf 1.2218 0 Td (Dev.)Tj /T1_2 1 Tf 2.4998 0 Td (15:)Tj /T1_0 1 Tf 1.6681 0 Td (2940)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2944.)Tj -18.998 -1.25 Td [(De)-235.1 (Smet,)-235.1 (C.,)-235.1 (De)-235.1 (Backer,)-235.1 (O.,)-235.1 (Faraoni,)-235.1 (I.,)-235.1 (Lurquin,)-235.1 (C.,)-235.1 (Brasseur,)-235.1 (F.,)]TJ 1.5 -1.25 Td [(and)-343.1 (Boon,)-343 (T.)-343 (1996.)-343 (The)-343.1 (activation)-343 (of)-343 (human)-343.1 (gene)-343 (MAGE-1)]TJ T* [(in)-481.5 (tumor)-481.5 (cells)-481.5 (is)-481.5 (correlated)-481.5 (with)-481.5 (genome-wide)-481.5 (demethyl-)]TJ T* (ation.)Tj /T1_1 1 Tf 2.9998 0 Td [(Proc.)-332.7 (Natl.)-332.7 (Acad.)-332.7 (Sci.)]TJ /T1_2 1 Tf 10.4441 0 Td (93:)Tj /T1_0 1 Tf 1.6681 0 Td (7149)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (7153.)Tj -16.612 -1.25 Td [(De)-224.8 (Smet,)-224.8 (C.,)-224.8 (Lurquin,)-224.8 (C.,)-224.8 (Lethe,)-224.8 (B.,)-224.8 (Martelange,)-224.8 (V.,)-224.8 (and)-224.8 (Boon,)-224.8 (T.)]TJ 1.5 -1.25 Td [(1999.)-219.5 (DNA)-219.5 (methylation)-219.5 (is)-219.5 (the)-219.5 (primary)-219.5 (silencing)-219.5 (mechanism)]TJ T* [(for)-291.2 (a)-291.2 (set)-291.2 (of)-291.2 (germ)-291.2 (line-)-291.2 (and)-291.2 (tumor-specific)-291.2 (genes)-291.2 (with)-291.2 (a)-291.2 (CpG-)]TJ T* [(rich)-332.8 (promoter.)]TJ /T1_1 1 Tf 7.0556 0 Td [(Mol.)-332.7 (Cell.)-332.7 (Biol.)]TJ /T1_2 1 Tf 7.4983 0 Td (11:)Tj /T1_0 1 Tf 1.6681 0 Td (7327)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (7335.)Tj -17.722 -1.25 Td [(Ehrlich,)-298.3 (M.)-298.3 (1982.)-298.3 (Amount)-298.3 (and)-298.3 (distribution)-298.3 (of)-298.3 (5-methycytosine)]TJ 1.5 -1.25 Td [(in)-559.7 (human)-559.7 (DNA)-559.7 (from)-559.7 (different)-559.7 (types)-559.7 (of)-559.7 (tissues)-559.7 (or)-559.7 (cells.)]TJ /T1_1 1 Tf T* [(Nucleic)-332.8 (Acids)-332.7 (Res.)]TJ /T1_2 1 Tf 9.2183 0 Td (10:)Tj /T1_0 1 Tf 1.6681 0 Td (2709)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2721.)Tj -12.3865 -1.25 Td [(Ferguson-Smith,)-440.7 (A.C.)-440.7 (and)-440.7 (Surani,)-440.7 (M.A.)-440.7 (2001.)-440.7 (Imprinting)-440.7 (and)]TJ 1.5 -1.25 Td [(the)-431.5 (epigenetic)-431.5 (asymmetry)-431.5 (between)-431.5 (parental)-431.5 (genomes.)]TJ /T1_1 1 Tf 26.0331 0 Td (Sci-)Tj -26.0331 -1.25 Td (ence)Tj /T1_2 1 Tf 2.4438 0 Td (293:)Tj /T1_0 1 Tf 2.2241 0 Td (1086)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1089.)Tj -6.1679 -1.25 Td [(Finnegan,)-219.5 (E.J.,)-219.5 (Peacock,)-219.5 (W.J.,)-219.5 (and)-219.5 (Dennis,)-219.5 (E.S.)-219.5 (2000.)-219.5 (DNA)-219.5 (meth-)]TJ 1.5 -1.25 Td [(ylation,)-293.7 (a)-293.7 (key)-293.7 (regulator)-293.7 (of)-293.7 (plant)-293.7 (development)-293.7 (and)-293.7 (other)-293.7 (pro-)]TJ T* (cesses.)Tj /T1_1 1 Tf 3.4428 0 Td [(Curr.)-332.7 (Opin.)-332.7 (Genet.)-332.7 (Dev.)]TJ /T1_2 1 Tf 11.7211 0 Td (10:)Tj /T1_0 1 Tf 1.6681 0 Td (217)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (223.)Tj -18.332 -1.25 Td [(Flatau,)-385.7 (E.,)-385.7 (Gonzales,)-385.7 (F.A.,)-385.7 (Michalowsky,)-385.7 (L.A.,)-385.7 (and)-385.7 (Jones,)-385.7 (P.A.)]TJ 1.5 -1.25 Td [(1984.)-258.5 (DNA)-258.5 (methylation)-258.5 (in)-258.5 (5-Aza-2)]TJ /T1_5 1 Tf [-0.3 (\001)]TJ /T1_0 1 Tf (-deoxycytidine-resistant)Tj T* [(variants)-336.7 (of)-336.7 (C3H)-336.7 (10T1/2)-336.7 (C18)-336.7 (cells.)]TJ /T1_1 1 Tf 16.4111 0 Td [(Mol.)-336.7 (Cell.)-336.6 (Biol.)]TJ /T1_2 1 Tf 7.51 0 Td (4:)Tj /T1_0 1 Tf 1.1121 0 Td (2098)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf -25.0332 -1.25 Td (2102.)Tj -1.5 -1.25 Td [(Francis,)-268.1 (N.J.)-268.1 (and)-268.1 (Kingston,)-268.1 (R.E.)-268.1 (2001.)-268.1 (Mechanisms)-268.1 (of)-268.1 (transcrip-)]TJ 1.5 -1.25 Td [(tional)-332.7 (memory.)]TJ /T1_1 1 Tf 7.5546 0 Td [(Nat.)-332.7 (Rev.)-332.7 (Mol.)-332.7 (Cell.)-332.7 (Biol.)]TJ /T1_2 1 Tf 12.2759 0 Td (2:)Tj /T1_0 1 Tf 1.1121 0 Td (409)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (421.)Tj -22.4426 -1.25 Td [(Fuks,)-566.4 (F.,)-566.4 (Burgers,)-566.4 (W.A.,)-566.4 (Brehm,)-566.4 (A.,)-566.4 (Hughes-Davies,)-566.4 (L.,)-566.4 (and)]TJ 1.5 -1.25 Td [(Kouzarides,)-264.9 (T.)-264.9 (2000.)-264.9 (DNA)-264.9 (methyltransferase)-264.9 (Dnmt1)-264.9 (associ-)]TJ T* [(ates)-393.5 (with)-393.5 (histone)-393.5 (deacetylase)-393.5 (activity.)]TJ /T1_1 1 Tf 18.5226 0 Td [(Nat.)-393.5 (Genet.)]TJ /T1_2 1 Tf 5.954 0 Td (24:)Tj /T1_0 1 Tf 1.6681 0 Td (88)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf -26.1447 -1.25 Td (91.)Tj -1.5 -1.25 Td [(Fuks,)-230.8 (F.,)-230.8 (Burgers,)-230.8 (W.A.,)-230.8 (Godin,)-230.8 (N.,)-230.8 (Kasai,)-230.8 (M.,)-230.8 (and)-230.8 (Kouzarides,)-230.8 (T.)]TJ 1.5 -1.25 Td [(2001.)-410.9 (Dnmt3a)-410.9 (binds)-410.9 (deacetylases)-410.9 (and)-410.9 (is)-410.9 (recruited)-410.9 (by)-410.9 (a)-410.9 (se-)]TJ T* [(quence-specific)-385.7 (repressor)-385.7 (to)-385.7 (silence)-385.7 (transcription.)]TJ /T1_1 1 Tf 23.6496 0 Td [(EMBO)-385.7 (J.)]TJ /T1_2 1 Tf -23.6496 -1.25 Td (20:)Tj /T1_0 1 Tf 1.6681 0 Td (2536)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2544.)Tj -3.1681 -1.25 Td [(Garrick,)-453.8 (D.,)-453.8 (Fiering,)-453.8 (S.,)-453.8 (Martin,)-453.8 (D.I.,)-453.8 (and)-453.8 (Whitelaw,)-453.8 (E.)-453.8 (1998.)]TJ 1.5 -1.25 Td [(Repeat-induced)-552.2 (gene)-552.2 (silencing)-552.2 (in)-552.2 (mammals.)]TJ /T1_1 1 Tf 22.0353 0 Td [(Nat.)-552.2 (Genet.)]TJ /T1_2 1 Tf -22.0353 -1.25 Td (18:)Tj /T1_0 1 Tf 1.6681 0 Td (56)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (59.)Tj -3.1681 -1.25 Td [(Gautsch,)-361.2 (J.W.)-361.2 (and)-361.2 (Wilson,)-361.2 (M.C.)-361.2 (1983.)-361.2 (Delayed)-361.2 (de)-361.2 (novo)-361.2 (meth-)]TJ 1.5 -1.25 Td [(ylation)-386 (in)-386 (teratocarcinoma)-386 (cells)-386 (suggests)-386 (additional)-386 (tissue-)]TJ T* [(specific)-246.8 (mechanisms)-246.8 (for)-246.8 (controlling)-246.8 (gene)-246.8 (expression.)]TJ /T1_1 1 Tf 24.4782 0 Td (Nature)Tj /T1_2 1 Tf -24.4782 -1.25 Td (301:)Tj /T1_0 1 Tf 2.2241 0 Td (32)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (37.)Tj -3.7241 -1.25 Td [(Gibbons,)-536.2 (R.J.,)-536.2 (McDowell,)-536.2 (T.L.,)-536.2 (Raman,)-536.2 (S.,)-536.2 (O)]TJ /T1_3 1 Tf [-0.4 (\222)]TJ /T1_0 1 Tf [(Rourke,)-536.2 (D.M.,)]TJ 1.5 -1.25 Td [(Garrick,)-318.2 (D.,)-318.2 (Ayyub,)-318.2 (H.,)-318.2 (and)-318.2 (Higgs,)-318.2 (D.R.)-318.2 (2000.)-318.2 (Mutations)-318.2 (in)]TJ /T1_2 1 Tf 6.9846 0 0 6.9846 428.4 755.2657 Tm [(DNA)-332.8 (methylation)-332.8 (and)-332.8 (epigenetic)-332.8 (memory)]TJ 2.6096 -101.2143 Td [(GENES)-332.8 (&)-332.8 (DEVELOPMENT)-3000 (17)]TJ ET BT /GS1 gs /T1_6 1 Tf 8 0 0 8 529.31177 806 Tm ( )Tj 0 0 1 rg /GS1 gs -16.44997 0 Td (Cold Spring Harbor Laboratory Press)Tj 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(DNA)-469.5 (methylation.)]TJ /T1_1 1 Tf 22.1195 0 Td [(Nat.)-469.5 (Genet.)]TJ /T1_2 1 Tf -22.1195 -1.25 Td (24:)Tj /T1_0 1 Tf 1.6681 0 Td (368)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (371.)Tj -3.1681 -1.25 Td [(Gowher,)-429.3 (H.)-429.3 (and)-429.3 (Jeltsch,)-429.3 (A.)-429.3 (2001.)-429.3 (Enzymatic)-429.3 (properties)-429.3 (of)-429.3 (re-)]TJ 1.5 -1.25 Td [(combinant)-507.1 (Dnmt3a)-507.1 (DNA)-507.1 (methyltransferase)-507.1 (from)-507.1 (mouse:)]TJ T* [(The)-282.3 (enzyme)-282.3 (modifies)-282.3 (DNA)-282.3 (in)-282.3 (a)-282.3 (non-processive)-282.3 (manner)-282.3 (and)]TJ T* [(also)-441.4 (methylates)-441.4 (non-CpG)-441.4 ([correction)-441.4 (of)-441.4 (non-CpA])-441.4 (sites.)]TJ /T1_1 1 Tf 27.1462 0 Td (J.)Tj -27.1462 -1.25 Td [(Mol.)-332.7 (Biol.)]TJ /T1_2 1 Tf 4.9436 0 Td (309:)Tj /T1_0 1 Tf 2.2241 0 Td (1201)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1208.)Tj -8.6677 -1.25 Td [(Gowher,)-353.3 (H.,)-353.3 (Leismann,)-353.3 (O.,)-353.3 (and)-353.3 (Jeltsch,)-353.3 (A.)-353.3 (2000.)-353.3 (DNA)-353.3 (of)]TJ /T1_1 1 Tf 27.1457 0 Td (Dro-)Tj -25.6457 -1.25 Td [(sophila)-407 (melanogaster)]TJ /T1_0 1 Tf 10.4811 0 Td [(contains)-407 (5-methylcytosine.)]TJ /T1_1 1 Tf 13.1471 0 Td [(EMBO)-407 (J.)]TJ /T1_2 1 Tf -23.6282 -1.25 Td (19:)Tj /T1_0 1 Tf 1.6681 0 Td (6918)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (6923.)Tj -3.1681 -1.25 Td [(Graves,)-357.2 (J.A.)-357.3 (1982.)-357.2 (5-Azacytidine-induced)-357.3 (re-expression)-357.3 (of)-357.2 (alle-)]TJ 1.5 -1.25 Td [(les)-420.1 (on)-420.1 (the)-420.1 (inactive)-420.1 (X)-420.1 (chromosome)-420.1 (in)-420.1 (a)-420.1 (hybrid)-420.1 (mouse)-420.1 (cell)]TJ T* (line.)Tj /T1_1 1 Tf 2.3878 0 Td [(Exp.)-332.7 (Cell)-332.7 (Res.)]TJ /T1_2 1 Tf 6.8873 0 Td (141:)Tj /T1_0 1 Tf 2.2241 0 Td (99)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (105.)Tj -12.9992 -1.25 Td [(Gurdon,)-468.8 (J.B.)-468.8 (1999.)-468.8 (Genetic)-468.8 (reprogramming)-468.8 (following)-468.8 (nuclear)]TJ 1.5 -1.25 Td [(transplantation)-866.8 (in)]TJ /T1_1 1 Tf 9.7888 0 Td (Amphibia)Tj /T1_0 1 Tf [-0.1 (.)]TJ /T1_1 1 Tf 5.8669 0 Td [(Semin.)-866.8 (Cell)-866.8 (Dev.)-866.8 (Biol.)]TJ /T1_2 1 Tf -15.6557 -1.25 Td (10:)Tj /T1_0 1 Tf 1.6681 0 Td (239)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (243.)Tj -3.1681 -1.25 Td [(Guy,)-469.8 (J.,)-469.8 (Hendrich,)-469.8 (B.,)-469.8 (Holmes,)-469.8 (M.,)-469.8 (Martin,)-469.8 (J.E.,)-469.8 (and)-469.8 (Bird,)-469.8 (A.)]TJ 1.5 -1.25 Td [(2001.)-514.9 (A)-514.9 (mouse)]TJ /T1_1 1 Tf 7.8798 0 Td (Mecp2)Tj /T1_0 1 Tf [(-null)-514.9 (mutation)-514.9 (causes)-514.9 (neurological)]TJ -7.8799 -1.25 Td [(symptoms)-233.3 (that)-233.3 (mimic)-233.3 (Rett)-233.3 (syndrome.)]TJ /T1_1 1 Tf 17.7768 0 Td [(Nat.)-233.3 (Genet.)]TJ /T1_0 1 Tf 5.6337 0 Td [(\(in)-233.3 (press\).)]TJ -24.9105 -1.25 Td [(Hansen,)-295.1 (R.S.,)-295.1 (Stoger,)-295.1 (R.,)-295.1 (Wijmenga,)-295.1 (C.,)-295.1 (Stanek,)-295.1 (A.M.,)-295.1 (Canfield,)]TJ 1.5 -1.25 Td [(T.K.,)-559 (Luo,)-559 (P.,)-559 (Matarazzo,)-559 (M.R.,)-559 (D)]TJ /T1_3 1 Tf (\222)Tj /T1_0 1 Tf [(Esposito,)-558.9 (M.,)-558.9 (Feil,)-558.9 (R.,)]TJ T* [(Gimelli,)-375.7 (G.,)-375.7 (et)-375.7 (al.)-375.7 (2000.)-375.7 (Escape)-375.7 (from)-375.7 (gene)-375.7 (silencing)-375.7 (in)-375.7 (ICF)]TJ T* [(syndrome:)-240.1 (Evidence)-240.1 (for)-240.1 (advanced)-240.1 (replication)-240.1 (time)-240.1 (as)-240.1 (a)-240.1 (major)]TJ T* (determinant.)Tj /T1_1 1 Tf 6.3328 0 Td [(Hum.)-332.7 (Mol.)-332.7 (Genet.)]TJ /T1_2 1 Tf 8.8863 0 Td (9:)Tj /T1_0 1 Tf 1.1121 0 Td (2575)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2587.)Tj -17.8313 -1.25 Td [(Hark,)-371.5 (A.T.,)-371.5 (Schoenherr,)-371.5 (C.J.,)-371.5 (Katz,)-371.5 (D.J.,)-371.5 (Ingram,)-371.5 (R.S.,)-371.5 (Levorse,)]TJ 1.5 -1.25 Td [(J.M.,)-544 (and)-544 (Tilghman,)-544 (S.M.)-544 (2000.)-544 (CTCF)-544 (mediates)-544 (methyl-)]TJ T* [(ation-sensitive)-474.1 (enhancer-blocking)-474.1 (activity)-474.1 (at)-474.1 (the)-474.1 (H19/Igf2)]TJ T* (locus.)Tj /T1_1 1 Tf 3.0548 0 Td (Nature)Tj /T1_2 1 Tf 3.6108 0 Td (405:)Tj /T1_0 1 Tf 2.2241 0 Td (486)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (489.)Tj -10.3897 -1.25 Td [(Harris,)-351.6 (M.)-351.6 (1982.)-351.6 (Induction)-351.6 (of)-351.6 (thymidine)-351.6 (kinase)-351.6 (in)-351.6 (enzyme-de-)]TJ 1.5 -1.25 Td [(ficient)-332.7 (Chinese)-332.8 (hamster)-332.8 (cells.)]TJ /T1_1 1 Tf 14.2722 0 Td (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (29:)Tj /T1_0 1 Tf 1.6681 0 Td (483)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (492.)Tj -19.717 -1.25 Td [(Hendrich,)-309.7 (B.)-309.7 (and)-309.7 (Bird,)-309.7 (A.)-309.7 (1998.)-309.7 (Identification)-309.7 (and)-309.7 (characteriza-)]TJ 1.5 -1.25 Td [(tion)-476.9 (of)-476.9 (a)-476.9 (family)-476.9 (of)-476.9 (mammalian)-476.9 (methyl-CpG)-476.9 (binding)-476.9 (pro-)]TJ T* (teins.)Tj /T1_1 1 Tf 2.8878 0 Td [(Mol.)-332.7 (Cell.)-332.7 (Biol.)]TJ /T1_2 1 Tf 7.4983 0 Td (18:)Tj /T1_0 1 Tf 1.6681 0 Td (6538)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (6547.)Tj -13.5542 -1.25 Td [(Hendrich,)-275.2 (B.,)-275.2 (Guy,)-275.2 (J.,)-275.2 (Ramsahoye,)-275.2 (B.,)-275.2 (Wilson,)-275.2 (V.A.,)-275.2 (and)-275.2 (Bird,)-275.2 (A.)]TJ 1.5 -1.25 Td [(2001.)-295.5 (Closely)-295.5 (related)-295.5 (proteins)-295.5 (Mbd2)-295.5 (and)-295.5 (Mbd3)-295.5 (play)-295.5 (distinc-)]TJ T* [(tive)-386.4 (but)-386.4 (interacting)-386.4 (roles)-386.4 (in)-386.4 (mouse)-386.4 (development.)]TJ /T1_1 1 Tf 23.5939 0 Td (Genes)Tj /T1_0 1 Tf 3.2744 0 Td (&)Tj /T1_1 1 Tf -26.8683 -1.25 Td (Dev.)Tj /T1_2 1 Tf 2.4998 0 Td (15:)Tj /T1_0 1 Tf 1.6681 0 Td (1613)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1618.)Tj -5.6679 -1.25 Td [(Hertz,)-312.1 (J.M.,)-312.1 (Schell,)-312.1 (G.,)-312.1 (and)-312.2 (Doerfler,)-312.1 (W.)-312.1 (1999.)-312.1 (Factors)-312.1 (affecting)]TJ 1.5 -1.25 Td [(de)-393.1 (novo)-393.1 (methylation)-393.1 (of)-393.1 (foreign)-393.1 (DNA)-393.1 (in)-393.1 (mouse)-393.1 (embryonic)]TJ T* [(stem)-332.8 (cells.)]TJ /T1_1 1 Tf 5.3306 0 Td [(J.)-332.7 (Biol.)-332.7 (Chem.)]TJ /T1_2 1 Tf 6.8873 0 Td (274:)Tj /T1_0 1 Tf 2.2241 0 Td (24232)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (24240.)Tj -15.942 -1.25 Td [(Holliday,)-483.3 (R.)-483.3 (and)-483.3 (Pugh,)-483.3 (J.E.)-483.3 (1975.)-483.3 (DNA)-483.3 (modification)-483.3 (mecha-)]TJ 1.5 -1.25 Td [(nisms)-811.1 (and)-811.1 (gene)-811.1 (activity)-811.1 (during)-811.1 (development.)]TJ /T1_1 1 Tf 24.2558 0 Td (Science)Tj /T1_2 1 Tf -24.2558 -1.25 Td (186:)Tj /T1_0 1 Tf 2.2241 0 Td (226)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (232.)Tj -3.7241 -1.25 Td [(Holmgren,)-371.5 (C.,)-371.5 (Kanduri,)-371.5 (C.,)-371.5 (Dell,)-371.5 (G.,)-371.5 (Ward,)-371.5 (A.,)-371.5 (Mukhopadhya,)]TJ 1.5 -1.25 Td [(R.,)-250.4 (Kanduri,)-250.4 (M.,)-250.4 (Lobanenkov,)-250.4 (V.,)-250.4 (and)-250.4 (Ohlsson,)-250.4 (R.)-250.4 (2001.)-250.4 (CpG)]TJ T* [(methylation)-542.6 (regulates)-542.6 (the)-542.6 (Igf2/H19)-542.6 (insulator.)]TJ /T1_1 1 Tf 22.6014 0 Td [(Curr.)-542.6 (Biol.)]TJ /T1_2 1 Tf -22.6014 -1.25 Td (11:)Tj /T1_0 1 Tf 1.6681 0 Td (1128)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1130.)Tj -3.1681 -1.25 Td [(Howell,)-219.5 (C.Y.,)-219.5 (Bestor,)-219.5 (T.H.,)-219.5 (Ding,)-219.5 (F.,)-219.5 (Latham,)-219.5 (K.E.,)-219.5 (Mertineit,)-219.5 (C.,)]TJ 1.5 -1.25 Td [(Trasler,)-417.6 (J.M.,)-417.6 (and)-417.6 (Chaillet,)-417.6 (J.R.)-417.6 (2001.)-417.6 (Genomic)-417.6 (imprinting)]TJ T* [(disrupted)-287.7 (by)-287.7 (a)-287.6 (maternal)-287.6 (effect)-287.6 (mutation)-287.7 (in)-287.6 (the)-287.7 (Dnmt1)-287.6 (gene.)]TJ /T1_1 1 Tf T* (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (104:)Tj /T1_0 1 Tf 2.2241 0 Td (829)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (838.)Tj -6.0009 -1.25 Td [(Hsieh,)-314.3 (C.-L.)-314.3 (1994.)-314.3 (Dependence)-314.3 (of)-314.3 (transcriptional)-314.3 (repression)-314.3 (on)]TJ 1.5 -1.25 Td [(CpG)-332.8 (methylation)-332.8 (density.)]TJ /T1_1 1 Tf 12.5544 0 Td [(Mol.)-332.7 (Cell.)-332.7 (Biol.)]TJ /T1_2 1 Tf 7.4983 0 Td (14:)Tj /T1_0 1 Tf 1.6681 0 Td (5487)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (5494.)Tj /T1_3 1 Tf -23.2208 -1.25 Td (\227\227\227)Tj /T1_0 1 Tf [(.)-393.1 (1999a.)-393.1 (Evidence)-393.1 (that)-393.1 (protein)-393.1 (binding)-393.1 (specifies)-393.1 (sites)-393.1 (of)]TJ 1.5 -1.25 Td [(DNA)-332.8 (demethylation.)]TJ /T1_1 1 Tf 10.2216 0 Td [(Mol.)-332.7 (Cell.)-332.7 (Biol.)]TJ /T1_2 1 Tf 7.4983 0 Td (19:)Tj /T1_0 1 Tf 1.6681 0 Td (46)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (56.)Tj /T1_3 1 Tf -20.8881 -1.25 Td (\227\227\227)Tj /T1_0 1 Tf [(.)-312.1 (1999b.)-312.1 (In)-312.2 (vivo)-312.2 (activity)-312.2 (of)-312.1 (murine)-312.2 (de)-312.2 (novo)-312.1 (methyltrans-)]TJ 1.5 -1.25 Td [(ferases,)-1366.5 (Dnmt3a)-1366.5 (and)-1366.5 (Dnmt3b.)]TJ /T1_1 1 Tf 18.5211 0 Td [(Mol.)-1366.5 (Cell.)-1366.5 (Biol.)]TJ /T1_2 1 Tf -18.5211 -1.25 Td (19:)Tj /T1_0 1 Tf 1.6681 0 Td (8211)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (8218.)Tj /T1_3 1 Tf -3.1681 -1.25 Td (\227\227\227)Tj /T1_0 1 Tf [(.)-512.4 (2000.)-512.4 (Dynamics)-512.4 (of)-512.4 (DNA)-512.4 (methylation)-512.4 (pattern.)]TJ /T1_1 1 Tf 26.8113 0 Td (Curr.)Tj -25.3114 -1.25 Td [(Opin.)-332.7 (Genet.)-332.7 (Dev.)]TJ /T1_2 1 Tf 8.9433 0 Td (10:)Tj /T1_0 1 Tf 1.6681 0 Td (224)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (228.)Tj -12.1115 -1.25 Td [(Hung,)-225.1 (M.S.,)-225.1 (Karthikeyan,)-225.1 (N.,)-225.1 (Huang,)-225.1 (B.,)-225.1 (Koo,)-225.1 (H.C.,)-225.1 (Kiger,)-225.1 (J.,)-225.1 (and)]TJ 1.5 -1.25 Td [(Shen,)-472.3 (C.J.)-472.3 (1999.)]TJ /T1_1 1 Tf 8.142 0 Td (Drosophila)Tj /T1_0 1 Tf 5.6394 0 Td [(proteins)-472.3 (related)-472.3 (to)-472.3 (vertebrate)]TJ -13.7814 -1.25 Td [(DNA)-292.3 (\(5-cytosine\))-292.3 (methyltransferases.)]TJ /T1_1 1 Tf 17.765 0 Td [(Proc.)-292.3 (Natl.)-292.3 (Acad.)-292.3 (Sci.)]TJ /T1_2 1 Tf -17.765 -1.25 Td (96:)Tj /T1_0 1 Tf 1.6681 0 Td (11940)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (11945.)Tj -3.1681 -1.25 Td [(Iida,)-460.6 (T.,)-460.6 (Nakahori,)-460.6 (Y.,)-460.6 (Tsutsumi,)-460.6 (O.,)-460.6 (Taketani,)-460.6 (Y.,)-460.6 (and)-460.6 (Nak-)]TJ 33.75 81.25 Td [(agome,)-270.6 (Y.)-270.6 (1994.)-270.6 (The)-270.6 (CpG)-270.6 (island)-270.6 (of)-270.6 (the)-270.6 (FMR-1)-270.6 (gene)-270.6 (is)-270.6 (meth-)]TJ T* [(ylated)-321 (differently)-321 (among)-321 (embryonic)-321 (tissues:)-321 (Implication)-321 (for)]TJ T* [(prenatal)-332.7 (diagnosis.)]TJ /T1_1 1 Tf 8.9986 0 Td [(Hum.)-332.7 (Reprod.)]TJ /T1_2 1 Tf 6.9436 0 Td (9:)Tj /T1_0 1 Tf 1.1121 0 Td (1471)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1473.)Tj -18.5543 -1.25 Td [(Issa,)-490.4 (J.P.)-490.4 (2000.)-490.4 (CpG-island)-490.4 (methylation)-490.4 (in)-490.4 (aging)-490.4 (and)-490.4 (cancer.)]TJ /T1_1 1 Tf 1.5 -1.25 Td [(Curr.)-332.7 (Top.)-332.7 (Microbiol.)-332.7 (Immunol.)]TJ /T1_2 1 Tf 15.3322 0 Td (249:)Tj /T1_0 1 Tf 2.2241 0 Td (101)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (118.)Tj -19.0563 -1.25 Td [(Jackson-Grusby,)-427.6 (L.,)-427.6 (Beard,)-427.6 (C.,)-427.6 (Possemat,)-427.6 (R.,)-427.6 (Tudor,)-427.6 (M.,)-427.6 (Fam-)]TJ 1.5 -1.25 Td [(brough,)-378.9 (D.,)-378.9 (Csankovszki,)-378.9 (G.,)-378.9 (Dausman,)-378.9 (J.,)-378.9 (Lee,)-378.9 (P.,)-378.9 (Wilson,)]TJ T* [(C.,)-521.7 (Lander,)-521.7 (E.,)-521.7 (et)-521.7 (al.)-521.7 (2001.)-521.7 (Loss)-521.7 (of)-521.7 (genomic)-521.7 (methylation)]TJ T* [(causes)-239.7 (p53-dependent)-239.7 (apoptosis)-239.7 (and)-239.7 (epigenetic)-239.7 (deregulation.)]TJ /T1_1 1 Tf T* [(Nat.)-332.7 (Genet.)]TJ /T1_2 1 Tf 5.8326 0 Td (27:)Tj /T1_0 1 Tf 1.6681 0 Td (31)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (39.)Tj -9.0007 -1.25 Td [(Jaenisch,)-615.8 (R.)-615.8 (1997.)-615.8 (DNA)-615.8 (methylation)-615.8 (and)-615.8 (imprinting:)-615.8 (Why)]TJ 1.5 -1.25 Td (bother?)Tj /T1_1 1 Tf 3.7778 0 Td [(Trends)-332.7 (Genet.)]TJ /T1_2 1 Tf 6.9986 0 Td (13:)Tj /T1_0 1 Tf 1.6681 0 Td (323)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (329.)Tj -13.9445 -1.25 Td [(Jaenisch,)-491.1 (R.,)-491.1 (Harbers,)-491.1 (K.,)-491.1 (Jahner,)-491.1 (D.,)-491.1 (Stewart,)-491.1 (C.,)-491.1 (and)-491.1 (Stuhl-)]TJ 1.5 -1.25 Td [(mann,)-496.4 (H.)-496.5 (1982.)-496.4 (DNA)-496.5 (methylation,)-496.5 (retroviruses,)-496.5 (and)-496.5 (em-)]TJ T* (bryogenesis.)Tj /T1_1 1 Tf 5.9998 0 Td [(J.)-332.7 (Cell)-332.7 (Biochem.)]TJ /T1_2 1 Tf 7.9423 0 Td (20:)Tj /T1_0 1 Tf 1.6681 0 Td (331)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (336.)Tj -17.1103 -1.25 Td [(Jaenisch,)-349.1 (R.,)-349.1 (Schnieke,)-349.1 (A.,)-349.1 (and)-349.1 (Harbers,)-349.1 (K.)-349.1 (1985.)-349.1 (Treatment)-349.1 (of)]TJ 1.5 -1.25 Td [(mice)-228.7 (with)-228.7 (5-azacytidine)-228.7 (efficiently)-228.7 (activates)-228.7 (silent)-228.7 (retroviral)]TJ T* [(genomes)-233 (in)-233 (different)-233 (tissues.)]TJ /T1_1 1 Tf 13.318 0 Td [(Proc.)-233 (Natl.)-233 (Acad.)-233 (Sci.)]TJ /T1_2 1 Tf 10.045 0 Td (82:)Tj /T1_0 1 Tf 1.6681 0 Td (1451)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf -25.0311 -1.25 Td (1455.)Tj -1.5 -1.25 Td [(Jeanpierre,)-386 (M.,)-386 (Turleau,)-386 (C.,)-386 (Aurias,)-386 (A.,)-386 (Prieur,)-386 (M.,)-386 (Ledeist,)-386 (F.,)]TJ 1.5 -1.25 Td [(Fischer,)-401.3 (A.,)-401.3 (and)-401.3 (Viegas-Pequignot,)-401.3 (E.)-401.3 (1993.)-401.3 (An)-401.3 (embryonic-)]TJ T* [(like)-463.1 (methylation)-463.1 (pattern)-463.1 (of)-463.1 (classical)-463.1 (satellite)-463.1 (DNA)-463.1 (is)-463.1 (ob-)]TJ T* [(served)-332.7 (in)-332.7 (ICF)-332.8 (syndrome.)]TJ /T1_1 1 Tf 11.7211 0 Td [(Hum.)-332.7 (Mol.)-332.7 (Genet.)]TJ /T1_2 1 Tf 8.8863 0 Td (2:)Tj /T1_0 1 Tf 1.1121 0 Td (731)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (735.)Tj -23.2196 -1.25 Td [(Jeddeloh,)-489.7 (J.A.,)-489.7 (Stokes,)-489.7 (T.L.,)-489.7 (and)-489.7 (Richards,)-489.7 (E.J.)-489.7 (1999.)-489.7 (Mainte-)]TJ 1.5 -1.25 Td [(nance)-422.2 (of)-422.2 (genomic)-422.2 (methylation)-422.2 (requires)-422.2 (a)-422.2 (SW12/SNF2-like)]TJ T* (protein.)Tj /T1_1 1 Tf 3.9448 0 Td [(Nat.)-332.7 (Genet.)]TJ /T1_2 1 Tf 5.8326 0 Td (22:)Tj /T1_0 1 Tf 1.6681 0 Td (94)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (97.)Tj -12.9455 -1.25 Td [(Jenuwein,)-238.3 (T.)-238.3 (and)-238.3 (Allis,)-238.3 (C.D.)-238.3 (2001.)-238.3 (Translating)-238.3 (the)-238.3 (histone)-238.3 (code.)]TJ /T1_1 1 Tf 1.5 -1.25 Td (Science)Tj /T1_2 1 Tf 3.8328 0 Td (293:)Tj /T1_0 1 Tf 2.2241 0 Td (1074)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1080.)Tj -7.5569 -1.25 Td [(Jones,)-245.4 (P.A.)-245.4 (and)-245.4 (Takai,)-245.4 (D.)-245.4 (2001.)-245.4 (The)-245.4 (role)-245.4 (of)-245.4 (DNA)-245.4 (methylation)-245.4 (in)]TJ 1.5 -1.25 Td [(mammalian)-332.8 (epigenetics.)]TJ /T1_1 1 Tf 11.7187 0 Td (Science)Tj /T1_2 1 Tf 3.8328 0 Td (293:)Tj /T1_0 1 Tf 2.2241 0 Td (1068)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1070.)Tj -19.2756 -1.25 Td [(Jones,)-358 (P.A.)-358 (and)-358 (Taylor,)-358 (S.M.)-358 (1980.)-358 (Cellular)-358 (differentiation,)-358 (cy-)]TJ 1.5 -1.25 Td [(tidine)-332.7 (analogues)-332.7 (and)-332.8 (DNA)-332.8 (methylation.)]TJ /T1_1 1 Tf 19.108 0 Td (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (20:)Tj /T1_0 1 Tf 1.6681 0 Td (85)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (93.)Tj -24.5528 -1.25 Td [(Jones,)-361.2 (P.A.,)-361.2 (Wolkowicz,)-361.2 (M.J.,)-361.2 (Rideout,)-361.2 (W.M.I.,)-361.2 (Gonzales,)-361.2 (F.A.,)]TJ 1.5 -1.25 Td [(Marziasz,)-371.1 (C.M.,)-371.1 (Coetzee,)-371.1 (G.A.,)-371.1 (and)-371.1 (Tapscott,)-371.1 (S.J.)-371.1 (1990.)-371.1 (De)]TJ T* [(novo)-349.4 (methylation)-349.4 (of)-349.4 (the)-349.4 (MyoD1)-349.4 (CpG)-349.4 (island)-349.4 (during)-349.4 (the)-349.4 (es-)]TJ T* [(tablishment)-448.9 (of)-448.9 (immortal)-448.9 (cell)-448.9 (lines.)]TJ /T1_1 1 Tf 17.2965 0 Td [(Proc.)-448.9 (Natl.)-448.9 (Acad.)-448.9 (Sci.)]TJ /T1_2 1 Tf -17.2965 -1.25 Td (87:)Tj /T1_0 1 Tf 1.6681 0 Td (6117)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (6121.)Tj -3.1681 -1.25 Td [(Jost,)-342.7 (J.P.,)-342.7 (Fremont,)-342.7 (M.,)-342.7 (Siegmann,)-342.7 (M.,)-342.7 (and)-342.7 (Hofsteenge,)-342.7 (J.)-342.7 (1997.)]TJ 1.5 -1.25 Td [(The)-394.5 (RNA)-394.5 (moiety)-394.5 (of)-394.5 (chick)-394.5 (embryo)-394.5 (5-methylcytosine-DNA)]TJ T* [(glycosylase)-274.5 (targets)-274.5 (DNA)-274.5 (demethylation.)]TJ /T1_1 1 Tf 18.9873 0 Td [(Nucleic)-274.5 (Acids)-274.5 (Res.)]TJ /T1_2 1 Tf -18.9873 -1.25 Td (25:)Tj /T1_0 1 Tf 1.6681 0 Td (4545)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (4550.)Tj -3.1681 -1.25 Td [(Jost,)-302.9 (J.P.,)-302.9 (Siegmann,)-302.9 (M.,)-302.9 (Thiry,)-302.9 (S.,)-302.9 (Jost,)-302.9 (Y.C.,)-302.9 (Benjamin,)-302.9 (D.,)-302.9 (and)]TJ 1.5 -1.25 Td [(Schwarz,)-261 (S.)-261 (1999.)-261 (A)-261 (re-investigation)-261 (of)-261 (the)-261 (ribonuclease)-261 (sen-)]TJ T* [(sitivity)-233.3 (of)-233.3 (a)-233.3 (DNA)-233.3 (demethylation)-233.3 (reaction)-233.3 (in)-233.3 (chicken)-233.3 (embryo)]TJ T* [(and)-332.8 (G8)-332.8 (mouse)-332.8 (myoblasts.)]TJ /T1_1 1 Tf 12.4421 0 Td [(FEBS)-332.7 (Lett.)]TJ /T1_2 1 Tf 5.2226 0 Td (449:)Tj /T1_0 1 Tf 2.2241 0 Td (251)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (254.)Tj -21.3888 -1.25 Td [(Juttermann,)-320 (R.,)-320 (Li,)-320 (E.,)-320 (and)-320 (Jaenisch,)-320 (R.)-320 (1994.)-320 (Toxicity)-320 (of)-320 (5-aza-)]TJ 1.5 -1.25 Td (2)Tj /T1_4 1 Tf (\001)Tj /T1_0 1 Tf [(-deoxycytidine)-330.3 (to)-330.3 (mammalian)-330.3 (cells)-330.3 (is)-330.3 (mediated)-330.3 (primarily)]TJ T* [(by)-322.1 (covalent)-322.1 (trapping)-322.1 (of)-322.1 (DNA)-322.1 (methyltransferase)-322.1 (rather)-322.1 (than)]TJ T* [(DNA)-1817.1 (demethylation.)]TJ /T1_1 1 Tf 13.1904 0 Td [(Proc.)-1817.1 (Natl.)-1817.1 (Acad.)-1817.1 (Sci.)]TJ /T1_2 1 Tf -13.1904 -1.25 Td (91:)Tj /T1_0 1 Tf 1.6681 0 Td (11797)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (11801.)Tj -3.1681 -1.25 Td [(Kafri,)-258.5 (T.,)-258.5 (Ariel,)-258.5 (M.,)-258.5 (Brandeis,)-258.5 (M.,)-258.5 (Shemer,)-258.5 (R.,)-258.5 (Urven,)-258.5 (L.,)-258.5 (McCar-)]TJ 1.5 -1.25 Td [(rey,)-237.6 (J.,)-237.6 (Cedar,)-237.6 (H.,)-237.6 (and)-237.6 (Razin,)-237.6 (A.)-237.6 (1992.)-237.6 (Developmental)-237.6 (pattern)]TJ T* [(of)-254.3 (gene-specific)-254.3 (DNA)-254.3 (methylation)-254.3 (in)-254.3 (the)-254.3 (mouse)-254.3 (embryo)-254.3 (and)]TJ T* [(germ)-332.8 (line.)]TJ /T1_1 1 Tf 5.0536 0 Td (Genes)Tj /T1_0 1 Tf 3.2208 0 Td (&)Tj /T1_1 1 Tf 1.2218 0 Td (Dev.)Tj /T1_2 1 Tf 2.4998 0 Td (6:)Tj /T1_0 1 Tf 1.1121 0 Td (705)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (714.)Tj -14.608 -1.25 Td [(Kang,)-347.3 (Y.K.,)-347.3 (Koo,)-347.3 (D.B.,)-347.3 (Park,)-347.3 (J.S.,)-347.3 (Choi,)-347.3 (Y.H.,)-347.3 (Chung,)-347.3 (A.S.,)-347.3 (Lee,)]TJ 1.5 -1.25 Td [(K.K.,)-364.7 (and)-364.7 (Han,)-364.7 (Y.M.)-364.7 (2001a.)-364.7 (Aberrant)-364.7 (methylation)-364.7 (of)-364.7 (donor)]TJ T* [(genome)-266 (in)-266 (cloned)-266 (bovine)-266 (embryos.)]TJ /T1_1 1 Tf 16.2761 0 Td [(Nat.)-266 (Genet.)]TJ /T1_2 1 Tf 5.699 0 Td (28:)Tj /T1_0 1 Tf 1.6681 0 Td (173)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (177.)Tj -25.1433 -1.25 Td [(Kang,)-280.5 (Y.K.,)-280.5 (Koo,)-280.5 (D.B.,)-280.5 (Park,)-280.5 (J.S.,)-280.5 (Choi,)-280.5 (Y.H.,)-280.5 (Kim,)-280.5 (H.N.,)-280.5 (Chang,)]TJ 1.5 -1.25 Td [(W.K.,)-448.2 (Lee,)-448.2 (K.K.,)-448.2 (and)-448.2 (Han,)-448.2 (Y.M.)-448.2 (2001b.)-448.2 (Typical)-448.2 (demethyl-)]TJ T* [(ation)-226.6 (events)-226.6 (in)-226.6 (cloned)-226.6 (pig)-226.6 (embryos.)-226.6 (Clues)-226.6 (on)-226.6 (species-specific)]TJ T* [(differences)-290.5 (in)-290.5 (epigenetic)-290.5 (reprogramming)-290.5 (of)-290.5 (cloned)-290.5 (donor)-290.5 (ge-)]TJ T* (nome.)Tj /T1_1 1 Tf 3.2218 0 Td [(J.)-332.7 (Biol.)-332.7 (Chem.)]TJ /T1_2 1 Tf 6.8873 0 Td (276:)Tj /T1_0 1 Tf 2.2241 0 Td (39980)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (39984.)Tj -13.8332 -1.25 Td [(Kass,)-237.9 (S.U.,)-237.9 (Landsberger,)-237.9 (N.,)-237.9 (and)-237.9 (Wolffe,)-237.9 (A.P.)-237.9 (1997a.)-237.9 (DNA)-237.9 (meth-)]TJ 1.5 -1.25 Td [(ylation)-329.9 (directs)-329.9 (a)-329.9 (time-dependent)-329.9 (repression)-329.9 (of)-329.9 (transcription)]TJ T* (initiation.)Tj /T1_1 1 Tf 4.9988 0 Td [(Curr.)-332.7 (Biol.)]TJ /T1_2 1 Tf 5.2775 0 Td (7:)Tj /T1_0 1 Tf 1.1121 0 Td (157)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (165.)Tj -12.8885 -1.25 Td [(Kass,)-369.7 (S.U.,)-369.7 (Pruss,)-369.7 (D.,)-369.7 (and)-369.7 (Wolffe,)-369.7 (A.P.)-369.7 (1997b.)-369.7 (How)-369.7 (does)-369.7 (DNA)]TJ /T1_2 1 Tf 6.9846 0 0 6.9846 75.5688 755.2657 Tm (Bird)Tj 0 -101.2143 TD [(18)-3000 (GENES)-332.8 (&)-332.8 (DEVELOPMENT)]TJ ET 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1 Tf 16.7082 0 Td [(Trends)-440 (Genet.)]TJ /T1_2 1 Tf 7.2131 0 Td (13:)Tj /T1_0 1 Tf 1.6681 0 Td (444)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf -25.5894 -1.25 Td (449.)Tj -1.5 -1.25 Td [(Keohane,)-281.3 (A.M.,)-281.3 (O)]TJ /T1_3 1 Tf (\222)Tj /T1_0 1 Tf [(Neill,)-281.3 (L.P.,)-281.3 (Belyaev,)-281.3 (N.D.,)-281.3 (Lavender,)-281.3 (J.S.,)-281.3 (and)]TJ 1.5 -1.25 Td [(Turner,)-401.6 (B.M.)-401.6 (1996.)-401.6 (X-inactivation)-401.6 (and)-401.6 (histone)-401.6 (H4)-401.6 (acetyla-)]TJ 0 -1.25 TD [(tion)-332.8 (in)-332.8 (embryonic)-332.8 (stem)-332.8 (cells.)]TJ /T1_1 1 Tf 14.1069 0 Td [(Dev.)-332.7 (Biol.)]TJ /T1_2 1 Tf 4.9995 0 Td (180:)Tj /T1_0 1 Tf 2.2241 0 Td (618)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (630.)Tj -22.8306 -1.25 Td [(Kondo,)-302.9 (T.,)-302.9 (Bobek,)-302.9 (M.P.,)-302.9 (Kuick,)-302.9 (R.,)-302.9 (Lamb,)-302.9 (B.,)-302.9 (Zhu,)-302.9 (X.,)-302.9 (Narayan,)]TJ 1.5 -1.25 Td [(A.,)-469.1 (Bourc)]TJ /T1_3 1 Tf [-0.1 (\222)]TJ /T1_0 1 Tf [(his,)-469.1 (D.,)-469.1 (Viegas-Pequignot,)-469.1 (E.,)-469.1 (Ehrlich,)-469.1 (M.,)-469.1 (et)-469.1 (al.)]TJ T* [(2000.)-514.6 (Whole-genome)-514.6 (methylation)-514.6 (scan)-514.6 (in)-514.6 (ICF)-514.6 (syndrome:)]TJ T* [(Hypomethylation)-450.3 (of)-450.3 (non-satellite)-450.3 (DNA)-450.3 (repeats)-450.3 (D4Z4)-450.3 (and)]TJ T* (NBL2.)Tj /T1_1 1 Tf 3.2778 0 Td [(Hum.)-332.7 (Mol.)-332.7 (Genet.)]TJ /T1_2 1 Tf 8.8863 0 Td (9:)Tj /T1_0 1 Tf 1.1121 0 Td (597)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (604.)Tj -14.7762 -1.25 Td [(Kress,)-314.3 (C.,)-314.3 (Thomassin,)-314.3 (H.,)-314.3 (and)-314.3 (Grange,)-314.3 (T.)-314.3 (2001.)-314.3 (Local)-314.3 (DNA)-314.3 (de-)]TJ 1.5 -1.25 Td [(methylation)-344.5 (in)-344.5 (vertebrates:)-344.5 (How)-344.5 (could)-344.5 (it)-344.5 (be)-344.5 (performed)-344.5 (and)]TJ T* (targeted?)Tj /T1_1 1 Tf 4.4998 0 Td [(FEBS)-332.8 (Lett.)]TJ /T1_2 1 Tf 5.2226 0 Td (494:)Tj /T1_0 1 Tf 2.2241 0 Td (135)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (140.)Tj -13.4465 -1.25 Td [(Laayoun,)-398.4 (A.)-398.4 (and)-398.4 (Smith,)-398.4 (S.S.)-398.4 (1995.)-398.4 (Methylation)-398.4 (of)-398.4 (slipped)-398.4 (du-)]TJ 1.5 -1.25 Td [(plexes,)-301.9 (snapbacks)-301.9 (and)-301.9 (cruciforms)-301.9 (by)-301.9 (human)-301.9 (DNA\(cytosine-)]TJ T* (5\)methyltransferase.)Tj /T1_1 1 Tf 9.7769 0 Td [(Nucleic)-332.7 (Acids)-332.7 (Res.)]TJ /T1_2 1 Tf 9.2184 0 Td (23:)Tj /T1_0 1 Tf 1.6681 0 Td (1584)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1589.)Tj -22.1634 -1.25 Td [(Lander,)-250 (E.S.,)-250 (Linton,)-250 (L.M.,)-250 (Birren,)-250 (B.,)-250 (Nusbaum,)-250 (C.,)-250 (Zody,)-250 (M.C.,)]TJ 1.5 -1.25 Td [(Baldwin,)-312.2 (J.,)-312.1 (Devon,)-312.2 (K.,)-312.1 (Dewar,)-312.1 (K.,)-312.1 (Doyle,)-312.1 (M.,)-312.2 (FitzHugh,)-312.1 (W.,)]TJ T* [(et)-467 (al.)-467 (2001.)-467 (Initial)-467 (sequencing)-467 (and)-467 (analysis)-467 (of)-467 (the)-467 (human)]TJ T* (genome.)Tj /T1_1 1 Tf 4.2218 0 Td (Nature)Tj /T1_2 1 Tf 3.6108 0 Td (409:)Tj /T1_0 1 Tf 2.2241 0 Td (860)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (921.)Tj -11.5567 -1.25 Td [(Lemon,)-404.8 (B.)-404.8 (and)-404.8 (Tjian,)-404.8 (R.)-404.8 (2000.)-404.8 (Orchestrated)-404.8 (response:)-404.8 (A)-404.8 (sym-)]TJ 1.5 -1.25 Td [(phony)-511 (of)-511 (transcription)-511 (factors)-511 (for)-511 (gene)-511 (control.)]TJ /T1_1 1 Tf 23.4684 0 Td (Genes)Tj /T1_0 1 Tf 3.3991 0 Td (&)Tj /T1_1 1 Tf -26.8674 -1.25 Td (Dev.)Tj /T1_2 1 Tf 2.4998 0 Td (14:)Tj /T1_0 1 Tf 1.6681 0 Td (2551)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2569.)Tj -5.6679 -1.25 Td [(Li,)-275.2 (E.,)-275.2 (Bestor,)-275.2 (T.H.,)-275.2 (and)-275.2 (Jaenisch,)-275.2 (R.)-275.2 (1992.)-275.2 (Targeted)-275.2 (mutation)-275.2 (of)]TJ 1.5 -1.25 Td [(the)-449.6 (DNA)-449.6 (methyltransferase)-449.6 (gene)-449.6 (results)-449.6 (in)-449.6 (embryonic)-449.6 (le-)]TJ T* (thality.)Tj /T1_1 1 Tf 3.7218 0 Td (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (69:)Tj /T1_0 1 Tf 1.6681 0 Td (915)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (926.)Tj -9.1667 -1.25 Td [(Li,)-351.2 (E.,)-351.2 (Beard,)-351.2 (C.,)-351.2 (and)-351.2 (Jaenisch,)-351.2 (R.)-351.2 (1993.)-351.2 (Role)-351.2 (for)-351.2 (DNA)-351.2 (methyl-)]TJ 1.5 -1.25 Td [(ation)-332.8 (in)-332.8 (genomic)-332.8 (imprinting.)]TJ /T1_1 1 Tf 13.8852 0 Td (Nature)Tj /T1_2 1 Tf 3.6108 0 Td (366:)Tj /T1_0 1 Tf 2.2241 0 Td (362)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (365.)Tj -21.2201 -1.25 Td [(Lin,)-269.9 (I.G.,)-269.9 (Tomzynski,)-269.9 (T.J.,)-269.9 (Ou,)-269.9 (Q.,)-269.9 (and)-269.9 (Hsieh,)-269.9 (C.L.)-269.9 (2000.)-269.9 (Modu-)]TJ 1.5 -1.25 Td [(lation)-275.2 (of)-275.2 (DNA)-275.2 (binding)-275.2 (protein)-275.2 (affinity)-275.2 (directly)-275.2 (affects)-275.2 (target)]TJ T* [(site)-332.8 (demethylation.)]TJ /T1_1 1 Tf 9.3876 0 Td [(Mol.)-332.7 (Cell.)-332.7 (Biol.)]TJ /T1_2 1 Tf 7.4983 0 Td (20:)Tj /T1_0 1 Tf 1.6681 0 Td (2343)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2349.)Tj -20.0541 -1.25 Td [(Liu,)-354.8 (W.M.,)-354.8 (Maraia,)-354.8 (R.J.,)-354.8 (Rubin,)-354.8 (C.M.,)-354.8 (and)-354.8 (Schmid,)-354.8 (C.W.)-354.8 (1994.)]TJ 1.5 -1.25 Td [(Alu)-404.1 (transcrips:)-404.1 (Cytoplasmic)-404.1 (localisation)-404.1 (and)-404.1 (regulation)-404.1 (by)]TJ T* [(DNA)-332.8 (methylation.)]TJ /T1_1 1 Tf 9.1656 0 Td [(Nucleic)-332.7 (Acids)-332.7 (Res.)]TJ /T1_2 1 Tf 9.2183 0 Td (22:)Tj /T1_0 1 Tf 1.6681 0 Td (1087)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1095.)Tj -21.5521 -1.25 Td [(Liu,)-243.6 (W.M.,)-243.6 (Chu,)-243.6 (W.M.,)-243.6 (Choudary,)-243.6 (P.V.,)-243.6 (and)-243.6 (Schmid,)-243.6 (C.W.)-243.6 (1995.)]TJ 1.5 -1.25 Td [(Cell)-376.8 (stress)-376.8 (and)-376.8 (translational)-376.8 (inhibitors)-376.8 (transiently)-376.8 (increase)]TJ T* [(the)-283 (abundance)-283 (of)-283 (mammalian)-283 (SINE)-283 (transcripts.)]TJ /T1_1 1 Tf 22.2525 0 Td [(Nucleic)-283 (Ac-)]TJ -22.2525 -1.25 Td [(ids)-332.7 (Res.)]TJ /T1_2 1 Tf 3.9975 0 Td (23:)Tj /T1_0 1 Tf 1.6681 0 Td (1758)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1765.)Tj -7.1657 -1.25 Td [(Lock,)-373.6 (L.F.,)-373.6 (Takagi,)-373.6 (N.,)-373.6 (and)-373.6 (Martin,)-373.6 (G.R.)-373.6 (1987.)-373.6 (Methylation)-373.6 (of)]TJ 1.5 -1.25 Td [(the)-417.3 (Hprt)-417.3 (gene)-417.3 (on)-417.3 (the)-417.3 (inactive)-417.3 (X)-417.3 (occurs)-417.3 (after)-417.3 (chromosome)]TJ T* (inactivation.)Tj /T1_1 1 Tf 6.2218 0 Td (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (48:)Tj /T1_0 1 Tf 1.6681 0 Td (39)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (46.)Tj -11.6667 -1.25 Td [(Lorincz,)-385.3 (M.C.,)-385.3 (Schubeler,)-385.3 (D.,)-385.3 (Goeke,)-385.3 (S.C.,)-385.3 (Walters,)-385.3 (M.,)-385.3 (Grou-)]TJ 1.5 -1.25 Td [(dine,)-312.2 (M.,)-312.2 (and)-312.2 (Martin,)-312.1 (D.I.K.)-312.1 (2000.)-312.1 (Dynamic)-312.2 (analysis)-312.1 (of)-312.1 (pro-)]TJ T* [(viral)-316.8 (induction)-316.8 (and)-316.8 (de)-316.8 (novo)-316.8 (methylation:)-316.8 (Implications)-316.8 (for)-316.8 (a)]TJ T* [(histone)-622.9 (deacetylase-independent,)-622.9 (methylation)-622.9 (density-de-)]TJ T* [(pendent)-265.3 (mechanism)-265.3 (of)-265.3 (transcriptional)-265.3 (repression.)]TJ /T1_1 1 Tf 23.1587 0 Td [(Mol.)-265.3 (Cell.)]TJ -23.1587 -1.25 Td (Biol.)Tj /T1_2 1 Tf 2.4998 0 Td (20:)Tj /T1_0 1 Tf 1.6681 0 Td (842)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (850.)Tj -5.6679 -1.25 Td [(Lyko,)-274.5 (F.,)-274.5 (Ramsahoye,)-274.5 (B.H.,)-274.5 (Kashevsky,)-274.5 (H.,)-274.5 (Tudor,)-274.5 (M.,)-274.5 (Mastran-)]TJ 1.5 -1.25 Td [(gelo,)-344.1 (M.-A.,)-344.1 (Orr-Weaver,)-344.1 (T.L.,)-344.1 (and)-344.1 (Jaenisch,)-344.1 (R.)-344.1 (1999.)-344.1 (Mam-)]TJ T* [(malian)-285.2 (\(cytosine-5\))-285.2 (methyltransferases)-285.2 (cause)-285.2 (genomic)-285.2 (DNA)]TJ T* [(methylation)-811.4 (and)-811.4 (lethality)-811.4 (in)]TJ /T1_1 1 Tf 15.5229 0 Td (Drosophila)Tj /T1_0 1 Tf [-0.1 (.)]TJ /T1_1 1 Tf 6.2565 0 Td [(Nat.)-811.4 (Genet.)]TJ /T1_2 1 Tf -21.7794 -1.25 Td (23:)Tj /T1_0 1 Tf 1.6681 0 Td (363)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (366.)Tj -3.1681 -1.25 Td [(Lyko,)-343 (F.,)-343 (Ramsahoye,)-343 (B.H.,)-343 (and)-343 (Jaenisch,)-343 (R.)-343 (2000.)-343 (DNA)-343.1 (meth-)]TJ 1.5 -1.25 Td [(ylation)-332.8 (in)]TJ /T1_1 1 Tf 4.8875 0 Td [(Drosophila)-332.7 (melanogaster)]TJ /T1_0 1 Tf [-0.2 (.)]TJ /T1_1 1 Tf 12.3886 0 Td (Nature)Tj /T1_2 1 Tf 3.6108 0 Td (408:)Tj /T1_0 1 Tf 2.2241 0 Td (538)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (540.)Tj -24.6111 -1.25 Td [(Lyle,)-386 (R.,)-386 (Watanabe,)-386 (D.,)-386 (te)-386 (Vruchte,)-386 (D.,)-386 (Lerchner,)-386 (W.,)-386 (Smrzka,)]TJ 1.5 -1.25 Td [(O.W.,)-361.2 (Wutz,)-361.2 (A.,)-361.2 (Schageman,)-361.2 (J.,)-361.2 (Hahner,)-361.2 (L.,)-361.2 (Davies,)-361.2 (C.,)-361.2 (and)]TJ T* [(Barlow,)-232.2 (D.P.)-232.3 (2000.)-232.2 (The)-232.3 (imprinted)-232.3 (antisense)-232.3 (RNA)-232.3 (at)-232.3 (the)-232.3 (Igf2r)]TJ T* [(locus)-601.2 (overlaps)-601.2 (but)-601.2 (does)-601.2 (not)-601.2 (imprint)-601.2 (Mas1.)]TJ /T1_1 1 Tf 21.9877 0 Td [(Nat.)-601.2 (Genet.)]TJ /T1_2 1 Tf -21.9877 -1.25 Td (25:)Tj /T1_0 1 Tf 1.6681 0 Td (19)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (21.)Tj -3.1681 -1.25 Td [(MacLeod,)-324.9 (D.,)-324.9 (Charlton,)-324.9 (J.,)-324.9 (Mullins,)-324.9 (J.,)-324.9 (and)-324.9 (Bird,)-324.9 (A.P.)-324.9 (1994.)-324.9 (Sp1)]TJ 1.5 -1.25 Td [(sites)-219.8 (in)-219.8 (the)-219.8 (mouse)]TJ /T1_1 1 Tf 8.4884 0 Td (aprt)Tj /T1_0 1 Tf 2.1098 0 Td [(gene)-219.8 (promoter)-219.8 (are)-219.8 (required)-219.8 (to)-219.8 (prevent)]TJ -10.5982 -1.25 Td [(methylation)-267.8 (of)-267.8 (the)-267.8 (CpG)-267.8 (island.)]TJ /T1_1 1 Tf 14.672 0 Td (Genes)Tj /T1_0 1 Tf 3.1558 0 Td (&)Tj /T1_1 1 Tf 1.1568 0 Td (Dev.)Tj /T1_2 1 Tf 2.4348 0 Td (8:)Tj /T1_0 1 Tf 1.1121 0 Td (2282)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2292.)Tj -24.0314 -1.25 Td [(MacLeod,)-286.2 (D.,)-286.2 (Ali,)-286.2 (R.R.,)-286.2 (and)-286.2 (Bird,)-286.2 (A.P.)-286.2 (1998.)-286.2 (An)-286.2 (alternative)-286.2 (pro-)]TJ 1.5 -1.25 Td [(moter)-240.8 (in)-240.8 (the)-240.8 (mouse)-240.8 (major)-240.8 (histocompatibility)-240.8 (cmplex)-240.8 (class)-240.8 (II)]TJ T* [(I-Ab)-374.3 (gene:)-374.3 (Implications)-374.3 (for)-374.3 (the)-374.3 (origin)-374.3 (of)-374.3 (CpG)-374.3 (islands.)]TJ /T1_1 1 Tf 25.6449 0 Td (Mol.)Tj -25.6449 -1.25 Td [(Cell.)-332.7 (Biol.)]TJ /T1_2 1 Tf 5.0546 0 Td (18:)Tj /T1_0 1 Tf 1.6681 0 Td (4433)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (4443.)Tj 24.0273 81.25 Td [(MacLeod,)-308.2 (D.,)-308.2 (Clark,)-308.2 (V.,)-308.2 (and)-308.2 (Bird,)-308.2 (A.)-308.2 (1999.)-308.2 (Absence)-308.3 (of)-308.3 (genome-)]TJ 1.5 -1.25 Td [(wide)-401.6 (changes)-401.6 (in)-401.6 (DNA)-401.6 (methylation)-401.6 (during)-401.6 (development)-401.6 (of)]TJ T* [(the)-332.7 (zebrafish)-332.7 (\()]TJ /T1_1 1 Tf [-0.2 (Danio)-332.7 (rerio)]TJ /T1_0 1 Tf [-0.1 (\).)]TJ /T1_1 1 Tf 12.8872 0 Td [(Nat.)-332.7 (Genet.)]TJ /T1_2 1 Tf 5.8326 0 Td (23:)Tj /T1_0 1 Tf 1.6681 0 Td (139)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (140.)Tj -21.8878 -1.25 Td [(Malik,)-247.5 (H.S.,)-247.5 (Burke,)-247.5 (W.D.,)-247.5 (and)-247.5 (Eickbush,)-247.5 (T.H.)-247.5 (1999.)-247.5 (The)-247.5 (age)-247.5 (and)]TJ 1.5 -1.25 Td [(evolution)-246.8 (of)-246.8 (non-LTR)-246.8 (retrotransposable)-246.8 (elements.)]TJ /T1_1 1 Tf 23.2344 0 Td [(Mol.)-246.8 (Biol.)]TJ -23.2344 -1.25 Td (Evol.)Tj /T1_2 1 Tf 2.6668 0 Td (16:)Tj /T1_0 1 Tf 1.6681 0 Td (793)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (805.)Tj -5.8349 -1.25 Td [(Martienssen,)-406.6 (R.A.)-406.6 (and)-406.6 (Colot,)-406.6 (V.)-406.6 (2001.)-406.6 (DNA)-406.6 (methylation)-406.6 (and)]TJ 1.5 -1.25 Td [(epigenetic)-338.8 (inheritance)-338.8 (in)-338.8 (plants)-338.8 (and)-338.8 (filamentous)-338.8 (fungi.)]TJ /T1_1 1 Tf 26.0348 0 Td (Sci-)Tj -26.0348 -1.25 Td (ence)Tj /T1_2 1 Tf 2.4438 0 Td (293:)Tj /T1_0 1 Tf 2.2241 0 Td (1070)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1074.)Tj -6.1679 -1.25 Td [(Matzke,)-256 (M.,)-256 (Matzke,)-256 (A.J.,)-256 (and)-256.1 (Kooter,)-256 (J.M.)-256 (2001.)-256 (RNA:)-256 (Guiding)]TJ 1.5 -1.25 Td [(gene)-332.7 (silencing.)]TJ /T1_1 1 Tf 7.2196 0 Td (Science)Tj /T1_2 1 Tf 3.8328 0 Td (293:)Tj /T1_0 1 Tf 2.2241 0 Td (1080)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1083.)Tj -14.7765 -1.25 Td [(Mayer,)-402.7 (W.,)-402.7 (Niveleau,)-402.7 (A.,)-402.7 (Walter,)-402.7 (J.,)-402.7 (Fundele,)-402.7 (R.,)-402.7 (and)-402.7 (Haaf,)-402.7 (T.)]TJ 1.5 -1.25 Td [(2000.)-441.1 (Demethylation)-441.1 (of)-441.1 (the)-441.1 (zygotic)-441.1 (paternal)-441 (genome.)]TJ /T1_1 1 Tf 26.0347 0 Td (Na-)Tj -26.0347 -1.25 Td (ture)Tj /T1_2 1 Tf 2.2218 0 Td (403:)Tj /T1_0 1 Tf 2.2241 0 Td (501)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (502.)Tj -5.9459 -1.25 Td [(McKeon,)-429 (C.,)-429 (Ohkubo,)-429 (H.,)-429 (Pastan,)-429 (I.,)-429 (and)-429 (de)-429 (Crombrugghe,)-429 (B.)]TJ 1.5 -1.25 Td [(1982.)-469.1 (Unusual)-469.1 (methylation)-469.1 (pattern)-469.1 (of)-469.1 (the)]TJ /T1_4 1 Tf 20.7049 0 Td (\001)Tj /T1_0 1 Tf 1.0801 0 Td [(2\(1\))-469.1 (collagen)]TJ -21.785 -1.25 Td (gene.)Tj /T1_1 1 Tf 2.7218 0 Td (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (29:)Tj /T1_0 1 Tf 1.6681 0 Td (203)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (210.)Tj -8.1667 -1.25 Td [(Miao,)-373.6 (V.P.,)-373.6 (Freitag,)-373.6 (M.,)-373.6 (and)-373.6 (Selker,)-373.6 (E.U.)-373.6 (2000.)-373.6 (Short)-373.6 (TpA-rich)]TJ 1.5 -1.25 Td [(segments)-226.2 (of)-226.2 (the)]TJ /T1_4 1 Tf 7.3997 0 Td (\003)Tj /T1_3 1 Tf (\226)Tj /T1_4 1 Tf (\004)Tj /T1_0 1 Tf 1.7812 0 Td [(region)-226.2 (induce)-226.2 (DNA)-226.2 (methylation)-226.2 (in)]TJ /T1_1 1 Tf 16.2973 0 Td (Neu-)Tj -25.4782 -1.25 Td [(rospora)-332.8 (crassa)]TJ /T1_0 1 Tf (.)Tj /T1_1 1 Tf 7.2785 0 Td [(J.)-332.7 (Mol.)-332.7 (Biol.)]TJ /T1_2 1 Tf 5.8873 0 Td (300:)Tj /T1_0 1 Tf 2.2241 0 Td (249)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (273.)Tj -16.89 -1.25 Td [(Miniou,)-413.7 (P.,)-413.7 (Jeanpierre,)-413.7 (M.,)-413.7 (Blanquet,)-413.7 (V.,)-413.7 (Sibella,)-413.7 (V.,)-413.7 (Bonneau,)]TJ 1.5 -1.25 Td [(D.,)-615.1 (Herbelin,)-615.1 (C.,)-615.1 (Fischer,)-615.1 (A.,)-615.1 (Niveleau,)-615.1 (A.,)-615.1 (and)-615.1 (Viegas-)]TJ T* [(Pequignot,)-393.5 (E.)-393.5 (1994.)-393.5 (Abnormal)-393.5 (methylation)-393.5 (pattern)-393.5 (in)-393.5 (con-)]TJ T* [(stitutive)-487.2 (and)-487.2 (facultative)-487.2 (\(X)-487.2 (inactive)-487.2 (chromosome\))-487.2 (hetero-)]TJ T* [(chromatin)-305.8 (of)-305.8 (ICF)-305.8 (patients.)]TJ /T1_1 1 Tf 12.6122 0 Td [(Hum.)-305.8 (Mol.)-305.8 (Genet.)]TJ /T1_2 1 Tf 8.8054 0 Td (3:)Tj /T1_0 1 Tf 1.1121 0 Td (2093)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2102.)Tj -24.0297 -1.25 Td [(Mohandas,)-337 (T.,)-337 (Sparkes,)-337 (R.S.,)-337 (and)-337 (Shapiro,)-337 (L.J.)-337 (1981a.)-337 (Reactiva-)]TJ 1.5 -1.25 Td [(tion)-411.2 (of)-411.2 (an)-411.2 (inactive)-411.2 (human)-411.2 (X)-411.2 (chromosome:)-411.2 (Evidence)-411.2 (for)-411.2 (X)]TJ T* [(inactivation)-332.7 (by)-332.8 (DNA)-332.7 (methylation.)]TJ /T1_1 1 Tf 16.5542 0 Td (Science)Tj /T1_2 1 Tf 3.8328 0 Td (211:)Tj /T1_0 1 Tf 2.2241 0 Td (393)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (396.)Tj /T1_3 1 Tf -24.1111 -1.25 Td (\227\227\227)Tj /T1_0 1 Tf [(.)-441.1 (1981b.)-441.1 (Reactivation)-441.1 (of)-441.1 (an)-441.1 (inactive)-441.1 (human)-441.1 (X-chromo-)]TJ 1.5 -1.25 Td [(some:)-227.3 (Evidence)-227.3 (for)-227.3 (X-inactivation)-227.3 (by)-227.3 (DNA)-227.3 (methylation.)]TJ /T1_1 1 Tf 26.0363 0 Td (Sci-)Tj -26.0363 -1.25 Td (ence)Tj /T1_2 1 Tf 2.4438 0 Td (211:)Tj /T1_0 1 Tf 2.2241 0 Td (393)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (396.)Tj -6.1679 -1.25 Td [(Monk,)-404.5 (M.,)-404.5 (Boubelik,)-404.5 (M.,)-404.5 (and)-404.5 (Lehnert,)-404.5 (S.)-404.5 (1987.)-404.5 (Temporal)-404.5 (and)]TJ 1.5 -1.25 Td [(regional)-268.1 (changes)-268.1 (in)-268.1 (DNA)-268.1 (methylation)-268.1 (in)-268.1 (the)-268.1 (embryonic,)-268.1 (ex-)]TJ T* [(traembryonic)-370 (and)-370 (germ)-370 (cell)-370 (lineages)-370 (during)-370 (mouse)-370 (embryo)]TJ T* (development.)Tj /T1_1 1 Tf 6.6118 0 Td (Development)Tj /T1_2 1 Tf 6.6108 0 Td (99:)Tj /T1_0 1 Tf 1.6681 0 Td (371)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (382.)Tj -16.3908 -1.25 Td [(Moore,)-318.5 (T.)-318.5 (and)-318.5 (Haig,)-318.5 (D.)-318.5 (1991.)-318.5 (Genomic)-318.5 (imprinting)-318.5 (in)-318.5 (mamma-)]TJ 1.5 -1.25 Td [(lian)-332.7 (development:)-332.7 (A)-332.8 (parental)-332.7 (tug-of-war.)]TJ /T1_1 1 Tf 19.331 0 Td (TIG)Tj /T1_2 1 Tf 2.2218 0 Td (7:)Tj /T1_0 1 Tf 1.1121 0 Td (1)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (4.)Tj -24.1648 -1.25 Td [(Mostoslavsky,)-250.4 (R.,)-250.4 (Singh,)-250.4 (N.,)-250.4 (Kirillov,)-250.4 (A.,)-250.4 (Pelanda,)-250.4 (R.,)-250.4 (Cedar,)-250.4 (H.,)]TJ 1.5 -1.25 Td [(Chess,)-429.3 (A.,)-429.3 (and)-429.3 (Bergman,)-429.3 (Y.)-429.3 (1998.)]TJ /T1_4 1 Tf 16.4672 0 Td (\005)Tj /T1_0 1 Tf 0.9853 0 Td [(chain)-429.3 (monoallelic)-429.3 (de-)]TJ -17.4525 -1.25 Td [(methylation)-645.3 (and)-645.3 (the)-645.2 (establishment)-645.2 (of)-645.2 (allelic)-645.2 (exclusion.)]TJ /T1_1 1 Tf T* (Genes)Tj /T1_0 1 Tf 3.2208 0 Td (&)Tj /T1_1 1 Tf 1.2218 0 Td (Dev.)Tj /T1_2 1 Tf 2.4998 0 Td (12:)Tj /T1_0 1 Tf 1.6681 0 Td (1801)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1811.)Tj -10.1104 -1.25 Td [(Mummaneni,)-460.2 (P.,)-460.2 (Bishop,)-460.2 (P.L.,)-460.2 (and)-460.2 (Turker,)-460.2 (M.S.)-460.2 (1993.)-460.2 (A)-460.2 (cis-)]TJ 1.5 -1.25 Td [(acting)-226.9 (element)-226.9 (accounts)-226.9 (for)-226.9 (a)-226.9 (conserved)-226.9 (methylation)-226.9 (pattern)]TJ T* [(upstream)-462.7 (of)-462.7 (the)-462.7 (mouse)-462.7 (adenine)-462.7 (phosphoribosyltransferase)]TJ T* (gene.)Tj /T1_1 1 Tf 2.7218 0 Td [(J.)-332.7 (Biol.)-332.7 (Chem.)]TJ /T1_2 1 Tf 6.8873 0 Td (268:)Tj /T1_0 1 Tf 2.2241 0 Td (552)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (558.)Tj -13.3332 -1.25 Td [(Mummaneni,)-448.2 (P.,)-448.2 (Yates,)-448.2 (P.,)-448.2 (Simpson,)-448.2 (J.,)-448.2 (Rose,)-448.2 (J.,)-448.2 (and)-448.2 (Turker,)]TJ 1.5 -1.25 Td [(M.S.)-268.8 (1998.)-268.8 (The)-268.8 (primary)-268.8 (function)-268.8 (of)-268.8 (a)-268.8 (redundant)-268.8 (Sp1)-268.8 (binding)]TJ T* [(site)-336.7 (in)-336.7 (the)-336.7 (mouse)-336.7 (aprt)-336.7 (gene)-336.7 (promoter)-336.7 (is)-336.7 (to)-336.7 (block)-336.7 (epigenetic)]TJ T* [(gene)-332.7 (inactivation.)]TJ /T1_1 1 Tf 8.6656 0 Td [(Nucleic)-332.7 (Acids)-332.7 (Res.)]TJ /T1_2 1 Tf 9.2183 0 Td (26:)Tj /T1_0 1 Tf 1.6681 0 Td (5163)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (5169.)Tj -21.0521 -1.25 Td [(Nakayama,)-355.1 (J.,)-355.1 (Rice,)-355.1 (J.C.,)-355.1 (Strahl,)-355.1 (B.D.,)-355.1 (Allis,)-355.1 (C.D.,)-355.1 (and)-355.1 (Grewal,)]TJ 1.5 -1.25 Td [(S.I.)-325.6 (2001.)-325.6 (Role)-325.6 (of)-325.6 (histone)-325.6 (H3)-325.6 (lysine)-325.6 (9)-325.6 (methylation)-325.7 (in)-325.7 (epige-)]TJ T* [(netic)-1073.2 (control)-1073.2 (of)-1073.2 (heterochromatin)-1073.2 (assembly.)]TJ /T1_1 1 Tf 24.2551 0 Td (Science)Tj /T1_2 1 Tf -24.2551 -1.25 Td (292:)Tj /T1_0 1 Tf 2.2241 0 Td (110)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (113.)Tj -3.7241 -1.25 Td [(Nan,)-469.8 (X.,)-469.8 (Meehan,)-469.8 (R.R.,)-469.8 (and)-469.8 (Bird,)-469.8 (A.)-469.8 (1993.)-469.8 (Dissection)-469.8 (of)-469.8 (the)]TJ 1.5 -1.25 Td [(methyl-CpG)-256.1 (binding)-256 (domain)-256 (from)-256.1 (the)-256 (chromosomal)-256 (protein)]TJ T* (MeCP2.)Tj /T1_1 1 Tf 4.0558 0 Td [(Nucleic)-332.8 (Acids)-332.7 (Res.)]TJ /T1_2 1 Tf 9.2183 0 Td (21:)Tj /T1_0 1 Tf 1.6681 0 Td (4886)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (4892.)Tj -16.4423 -1.25 Td [(Nan,)-371.1 (X.,)-371.1 (Campoy,)-371.1 (J.,)-371.1 (and)-371.1 (Bird,)-371.1 (A.)-371.1 (1997.)-371.1 (MeCP2)-371.1 (is)-371.1 (a)-371.1 (transcrip-)]TJ 1.5 -1.25 Td [(tional)-552.9 (repressor)-552.9 (with)-552.9 (abundant)-552.9 (binding)-552.9 (sites)-552.9 (in)-552.9 (genomic)]TJ T* (chromatin.)Tj /T1_1 1 Tf 5.4438 0 Td (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (88:)Tj /T1_0 1 Tf 1.6681 0 Td (471)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (481.)Tj -10.8887 -1.25 Td [(Niwa,)-375.4 (O.,)-375.4 (Yokota,)-375.4 (Y.,)-375.4 (Ishida,)-375.4 (H.,)-375.4 (and)-375.4 (Sugahara,)-375.4 (T.)-375.4 (1983.)-375.4 (Inde-)]TJ 1.5 -1.25 Td [(pendent)-904.1 (mechanisms)-904.1 (involved)-904.1 (in)-904.1 (suppression)-904.1 (of)-904.1 (the)]TJ T* [(Moloney)-385.7 (leukaemia)-385.7 (virus)-385.7 (genome)-385.7 (during)-385.7 (differentiation)-385.7 (of)]TJ T* [(murine)-332.7 (teratocarinoma)-332.8 (cells.)]TJ /T1_1 1 Tf 13.8304 0 Td (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (32:)Tj /T1_0 1 Tf 1.6681 0 Td (1105)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1113.)Tj -19.2753 -1.25 Td [(Noma,)-479 (K.,)-479.1 (Allis,)-479.1 (C.D.,)-479.1 (and)-479.1 (Grewal,)-479 (S.I.)-479.1 (2001.)-479 (Transitions)-479.1 (in)]TJ 1.5 -1.25 Td [(distinct)-306.5 (histone)-306.5 (H3)-306.5 (methylation)-306.5 (patterns)-306.5 (at)-306.5 (the)-306.5 (heterochro-)]TJ T* [(matin)-332.7 (domain)-332.7 (boundaries.)]TJ /T1_1 1 Tf 12.6094 0 Td (Science)Tj /T1_2 1 Tf 3.8328 0 Td (293:)Tj /T1_0 1 Tf 2.2241 0 Td (1150)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1155.)Tj /T1_2 1 Tf 6.9846 0 0 6.9846 428.4 755.2657 Tm [(DNA)-332.8 (methylation)-332.8 (and)-332.8 (epigenetic)-332.8 (memory)]TJ 2.6096 -101.2143 Td [(GENES)-332.8 (&)-332.8 (DEVELOPMENT)-3000 (19)]TJ ET BT /GS1 gs /T1_5 1 Tf 8 0 0 8 529.31177 806 Tm ( )Tj 0 0 1 rg /GS1 gs -16.44997 0 Td (Cold Spring Harbor Laboratory Press)Tj 0 g /GS1 gs -15.843 0 Td ( on August 22, 2022 - Published by )Tj 0 0 1 rg /GS1 gs -8.67099 0 Td (genesdev.cshlp.org)Tj 0 g /GS1 gs -8.11398 0 Td (Downloaded from )Tj ET endstream endobj 148 0 obj << /BG2 /Default /OP false /OPM 0 /SA false /SM 1 /TR2 /Default /UCR2 /Default /op false >> endobj 149 0 obj [ 150 0 R 152 0 R ] endobj 150 0 obj << /A 151 0 R /Border [ 0 0 0 ] /Rect [ 200.6 804 271.968 814 ] /Subtype /Link /Type /Annot >> endobj 151 0 obj << /S /URI /URI (http\072\057\057genesdev\056cshlp\056org\057) >> endobj 152 0 obj << /A 153 0 R /Border [ 0 0 0 ] /Rect [ 396.712 804 530.312 814 ] /Subtype /Link /Type /Annot >> endobj 153 0 obj << /S /URI /URI (http\072\057\057www\056cshlpress\056com) >> endobj 154 0 obj << /Length 20585 >> stream BT /GS0 gs /T1_0 1 Tf 7.9824 0 0 7.9824 75.5688 727.3275 Tm [(Okano,)-325.3 (M.,)-325.3 (Xie,)-325.3 (S.,)-325.3 (and)-325.3 (Li,)-325.3 (E.)-325.3 (1998a.)-325.3 (Cloning)-325.3 (and)-325.3 (characteriza-)]TJ 1.5 -1.25 Td [(tion)-573.9 (of)-573.9 (a)-573.9 (family)-573.9 (of)-573.9 (novel)-573.9 (mammalian)-573.9 (DNA)-573.9 (\(cytosine-5\))]TJ 0 -1.25 TD (methyltransferases.)Tj /T1_1 1 Tf 9.3869 0 Td [(Nat.)-332.7 (Genet.)]TJ /T1_2 1 Tf 5.8326 0 Td (19:)Tj /T1_0 1 Tf 1.6681 0 Td (219)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (220.)Tj /T1_3 1 Tf -18.3875 -1.25 Td (\227\227\227)Tj /T1_0 1 Tf [(.)-353 (1998b.)-353 (Dnmt2)-353 (is)-353 (not)-353 (required)-353 (for)-353 (de)-353 (novo)-353 (and)-353 (mainte-)]TJ 1.5 -1.25 Td [(nance)-407.3 (methylation)-407.3 (of)-407.3 (viral)-407.3 (DNA)-407.3 (in)-407.3 (embryonic)-407.3 (stem)-407.3 (cells.)]TJ /T1_1 1 Tf T* [(Nucleic)-332.7 (Acids)-332.7 (Res.)]TJ /T1_2 1 Tf 9.2184 0 Td (26:)Tj /T1_0 1 Tf 1.6681 0 Td (2536)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2540.)Tj -12.3865 -1.25 Td [(Okano,)-229.8 (M.,)-229.8 (Bell,)-229.8 (D.W.,)-229.8 (Haber,)-229.8 (D.A.,)-229.8 (and)-229.8 (Li,)-229.8 (E.)-229.8 (1999.)-229.8 (DNA)-229.8 (meth-)]TJ 1.5 -1.25 Td [(yltransferases)-247.5 (Dnmt3a)-247.5 (and)-247.5 (Dnmt3b)-247.5 (are)-247.5 (essential)-247.5 (for)-247.5 (de)-247.5 (novo)]TJ T* [(methylation)-1633.5 (and)-1633.5 (mammalian)-1633.5 (development.)]TJ /T1_1 1 Tf 25.8114 0 Td (Cell)Tj /T1_2 1 Tf -25.8114 -1.25 Td (99:)Tj /T1_0 1 Tf 1.6681 0 Td (247)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (257.)Tj -3.1681 -1.25 Td [(Oswald,)-358.3 (J.,)-358.3 (Engemann,)-358.3 (S.,)-358.3 (Lane,)-358.3 (N.,)-358.3 (Mayer,)-358.3 (W.,)-358.3 (Olek,)-358.3 (A.,)-358.3 (Fun-)]TJ 1.5 -1.25 Td [(dele,)-480.5 (R.,)-480.5 (Dean,)-480.5 (W.,)-480.5 (Reik,)-480.5 (W.,)-480.5 (and)-480.5 (Walter,)-480.5 (J.)-480.5 (2000.)-480.5 (Active)]TJ T* [(demethylation)-302.6 (of)-302.6 (the)-302.6 (paternal)-302.6 (genome)-302.6 (in)-302.6 (the)-302.6 (mouse)-302.6 (zygote.)]TJ /T1_1 1 Tf T* [(Curr.)-332.7 (Biol.)]TJ /T1_2 1 Tf 5.2776 0 Td (10:)Tj /T1_0 1 Tf 1.6681 0 Td (475)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (478.)Tj -8.4457 -1.25 Td [(Pannell,)-422.9 (D.,)-422.9 (Osborne,)-422.9 (C.S.,)-422.9 (Yao,)-422.9 (S.,)-422.9 (Sukonnik,)-422.9 (T.,)-422.9 (Pasceri,)-422.9 (P.,)]TJ 1.5 -1.25 Td [(Karaiskakis,)-318.5 (A.,)-318.5 (Okano,)-318.5 (M.,)-318.5 (Li,)-318.5 (E.,)-318.5 (Lipshitz,)-318.5 (H.D.,)-318.5 (and)-318.6 (Ellis,)]TJ T* [(J.)-476.2 (2000.)-476.2 (Retrovirus)-476.2 (vector)-476.2 (silencing)-476.2 (is)-476.2 (de)-476.2 (novo)-476.2 (methylase)]TJ T* [(independent)-686.8 (and)-686.8 (marked)-686.8 (by)-686.8 (a)-686.8 (repressive)-686.8 (histone)-686.8 (code.)]TJ /T1_1 1 Tf T* [(EMBO)-332.8 (J.)]TJ /T1_2 1 Tf 4.3875 0 Td (19:)Tj /T1_0 1 Tf 1.6681 0 Td (5884)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (5894.)Tj -7.5557 -1.25 Td [(Panning,)-365.1 (B.)-365.1 (and)-365.1 (Jaenisch,)-365.1 (R.)-365.1 (1996.)-365.1 (DNA)-365.1 (hypomethylation)-365.1 (can)]TJ 1.5 -1.25 Td [(activate)-226.9 (Xist)-226.9 (expression)-226.9 (and)-226.9 (silence)-226.9 (X-linked)-226.9 (genes.)]TJ /T1_1 1 Tf 23.7528 0 Td (Genes)Tj /T1_0 1 Tf 3.115 0 Td (&)Tj /T1_1 1 Tf -26.8677 -1.25 Td (Dev.)Tj /T1_2 1 Tf 2.4998 0 Td (10:)Tj /T1_0 1 Tf 1.6681 0 Td (1991)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2002.)Tj -5.6679 -1.25 Td [(Paro,)-355.1 (R.,)-355.1 (Strutt,)-355.1 (H.,)-355.1 (and)-355.1 (Cavalli,)-355.1 (G.)-355.1 (1998.)-355.1 (Heritable)-355.1 (chromatin)]TJ 1.5 -1.25 Td [(states)-371.8 (induced)-371.8 (by)-371.8 (the)-371.8 (Polycomb)-371.8 (and)-371.8 (trithorax)-371.8 (group)-371.8 (genes.)]TJ /T1_1 1 Tf T* [(Novartis)-332.7 (Found.)-332.7 (Symp.)]TJ /T1_2 1 Tf 11.1674 0 Td (214:)Tj /T1_0 1 Tf 2.2241 0 Td (51)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (61.)Tj -14.8915 -1.25 Td [(Pfeifer,)-281.6 (G.P.,)-281.6 (Steigerwald,)-281.6 (S.D.,)-281.6 (Hansen,)-281.6 (R.S.,)-281.6 (Gartler,)-281.6 (S.M.,)-281.6 (and)]TJ 1.5 -1.25 Td [(Riggs,)-320.3 (A.D.)-320.3 (1990.)-320.3 (Polymerase)-320.3 (chain)-320.3 (reaction-aided)-320.3 (genomic)]TJ T* [(sequencing)-362.2 (of)-362.2 (an)-362.2 (X)-362.2 (chromosome-linked)-362.2 (CpG)-362.2 (island:)-362.2 (Meth-)]TJ T* [(ylation)-521 (patterns)-521 (suggest)-521 (clonal)-521 (inheritance,)-521 (CpG)-521 (site)-521 (au-)]TJ T* [(tonomy,)-316.4 (and)-316.4 (an)-316.4 (explanation)-316.4 (of)-316.4 (activity)-316.4 (state)-316.4 (stability.)]TJ /T1_1 1 Tf 25.4226 0 Td (Proc.)Tj -25.4226 -1.25 Td [(Nat.)-332.7 (Acad.)-332.7 (Sci.)]TJ /T1_2 1 Tf 7.4443 0 Td (87:)Tj /T1_0 1 Tf 1.6681 0 Td (8252)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (8256.)Tj -10.6124 -1.25 Td [(Pirrotta,)-386 (V.)-386 (1999.)-386 (Polycomb)-386 (silencing)-386 (and)-386 (the)-386 (maintenance)-386 (of)]TJ 1.5 -1.25 Td [(stable)-282.7 (chromatin)-282.7 (states.)]TJ /T1_1 1 Tf 11.3472 0 Td [(Results)-282.7 (Probl.)-282.7 (Cell.)-282.7 (Differ.)]TJ /T1_2 1 Tf 12.5729 0 Td (25:)Tj /T1_0 1 Tf 1.6681 0 Td (205)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf -25.5881 -1.25 Td (228.)Tj -1.5 -1.25 Td [(Pollack,)-402.7 (Y.,)-402.7 (Stein,)-402.7 (R.,)-402.7 (Razin,)-402.7 (A.,)-402.7 (and)-402.7 (Cedar,)-402.7 (H.)-402.7 (1980.)-402.7 (Methyl-)]TJ 1.5 -1.25 Td [(ation)-434.7 (of)-434.7 (foreign)-434.7 (DNA)-434.7 (sequences)-434.7 (in)-434.7 (eukaryotic)-434.7 (cells.)]TJ /T1_1 1 Tf 25.4206 0 Td (Proc.)Tj -25.4206 -1.25 Td [(Natl.)-332.7 (Acad.)-332.7 (Sci.)]TJ /T1_2 1 Tf 7.7773 0 Td (77:)Tj /T1_0 1 Tf 1.6681 0 Td (6463)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (6467.)Tj -10.9454 -1.25 Td [(Poux,)-472.3 (S.,)-472.3 (McCabe,)-472.3 (D.,)-472.3 (and)-472.3 (Pirrotta,)-472.3 (V.)-472.3 (2001.)-472.3 (Recruitment)-472.3 (of)]TJ 1.5 -1.25 Td [(components)-496.5 (of)-496.5 (Polycomb)-496.5 (Group)-496.5 (chromatin)-496.5 (complexes)-496.5 (in)]TJ /T1_1 1 Tf T* (Drosophila)Tj /T1_0 1 Tf [-0.1 (.)]TJ /T1_1 1 Tf 5.7778 0 Td (Development)Tj /T1_2 1 Tf 6.6108 0 Td (128:)Tj /T1_0 1 Tf 2.2241 0 Td (75)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (85.)Tj -16.1128 -1.25 Td [(Pradhan,)-472.3 (S.,)-472.3 (Bacolla,)-472.3 (A.,)-472.3 (Wells,)-472.3 (R.D.,)-472.3 (and)-472.3 (Roberts,)-472.3 (R.J.)-472.3 (1999.)]TJ 1.5 -1.25 Td [(Recombinant)-240.4 (human)-240.4 (DNA)-240.4 (\(cytosine-5\))-240.4 (methyltransferase.)-240.4 (I.)]TJ T* [(Expression,)-544.4 (purification,)-544.4 (and)-544.4 (comparison)-544.4 (of)-544.4 (de)-544.4 (novo)-544.4 (and)]TJ T* [(maintenance)-261.4 (methylation.)]TJ /T1_1 1 Tf 12.5219 0 Td [(J.)-261.4 (Biol.)-261.4 (Chem.)]TJ /T1_2 1 Tf 6.6732 0 Td (274:)Tj /T1_0 1 Tf 2.2241 0 Td (33002)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (33010.)Tj -22.9192 -1.25 Td [(Prokhortchouk,)-599.4 (A.,)-599.4 (Hendrich,)-599.4 (B.,)-599.4 (Jorgensen,)-599.4 (H.,)-599.4 (Ruzov,)-599.4 (A.,)]TJ 1.5 -1.25 Td [(Wilm,)-517.4 (M.,)-517.4 (Georgiev,)-517.4 (G.,)-517.4 (Bird,)-517.4 (A.,)-517.4 (and)-517.4 (Prokhortchouk,)-517.4 (E.)]TJ T* [(2001.)-225.9 (The)-225.9 (p120)-225.9 (catenin)-225.9 (partner)-225.9 (Kaiso)-225.9 (is)-225.9 (a)-225.9 (DNA)-225.9 (methylation-)]TJ T* [(dependent)-227.3 (transcriptional)-227.3 (repressor.)]TJ /T1_1 1 Tf 16.7391 0 Td (Genes)Tj /T1_0 1 Tf 3.1153 0 Td (&)Tj /T1_1 1 Tf 1.1163 0 Td (Dev.)Tj /T1_2 1 Tf 2.3943 0 Td (15:)Tj /T1_0 1 Tf 1.6681 0 Td (1613)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf -25.0331 -1.25 Td (1618.)Tj -1.5 -1.25 Td [(Ramchandani,)-302.2 (S.,)-302.2 (Bhattacharya,)-302.2 (S.K.,)-302.2 (Cervoni,)-302.2 (N.,)-302.2 (and)-302.2 (Szyf,)-302.2 (M.)]TJ 1.5 -1.25 Td [(1999.)-536.6 (DNA)-536.6 (methylation)-536.6 (is)-536.6 (a)-536.6 (reversible)-536.6 (biological)-536.6 (signal.)]TJ /T1_1 1 Tf T* [(Proc.)-332.7 (Natl.)-332.7 (Acad.)-332.7 (Sci.)]TJ /T1_2 1 Tf 10.4441 0 Td (96:)Tj /T1_0 1 Tf 1.6681 0 Td (6107)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (6112.)Tj -13.6122 -1.25 Td [(Ramsahoye,)-399.9 (B.H.,)-399.9 (Biniszkiewicz,)-399.9 (D.,)-399.9 (Lyko,)-399.9 (F.,)-399.9 (Clark,)-399.9 (V.,)-399.9 (Bird,)]TJ 1.5 -1.25 Td [(A.P.,)-295.5 (and)-295.5 (Jaenisch,)-295.5 (R.)-295.5 (2000.)-295.5 (Non-CpG)-295.5 (methylation)-295.5 (is)-295.5 (preva-)]TJ T* [(lent)-303.3 (in)-303.3 (embryonic)-303.3 (stem)-303.3 (cells)-303.3 (and)-303.3 (may)-303.3 (be)-303.3 (mediated)-303.3 (by)-303.3 (DNA)]TJ T* [(methyltransferase)-332.8 (3a.)]TJ /T1_1 1 Tf 10.3316 0 Td [(Proc.)-332.7 (Natl.)-332.7 (Acad.)-332.7 (Sci.)]TJ /T1_2 1 Tf 10.4441 0 Td (97:)Tj /T1_0 1 Tf 1.6681 0 Td (5237)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (5242.)Tj -23.9439 -1.25 Td [(Reik,)-392.8 (W.)-392.8 (and)-392.8 (Walter,)-392.8 (J.)-392.8 (2001.)-392.8 (Evolution)-392.8 (of)-392.8 (imprinting)-392.8 (mecha-)]TJ 1.5 -1.25 Td [(nisms:)-464.5 (The)-464.5 (battle)-464.5 (of)-464.5 (the)-464.5 (sexes)-464.5 (begins)-464.5 (in)-464.5 (the)-464.5 (zygote.)]TJ /T1_1 1 Tf 25.6992 0 Td (Nat.)Tj -25.6992 -1.25 Td (Genet.)Tj /T1_2 1 Tf 3.4438 0 Td (27:)Tj /T1_0 1 Tf 1.6681 0 Td (255)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (256.)Tj -6.6119 -1.25 Td [(Reik,)-324.2 (W.,)-324.2 (Dean,)-324.2 (W.,)-324.2 (and)-324.2 (Walter,)-324.2 (J.)-324.2 (2001.)-324.2 (Epigenetic)-324.2 (reprogram-)]TJ 1.5 -1.25 Td [(ming)-317.1 (in)-317.1 (mammalian)-317.1 (development.)]TJ /T1_1 1 Tf 16.4887 0 Td (Science)Tj /T1_2 1 Tf 3.8172 0 Td (293:)Tj /T1_0 1 Tf 2.2241 0 Td (1089)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1093.)Tj -24.03 -1.25 Td [(Rhee,)-280.9 (I.,)-280.9 (Jair,)-280.9 (K.W.,)-280.9 (Yen,)-280.9 (R.W.,)-280.9 (Lengauer,)-280.9 (C.,)-280.9 (Herman,)-280.9 (J.G.,)-280.9 (Kin-)]TJ 1.5 -1.25 Td [(zler,)-455.3 (K.W.,)-455.3 (Vogelstein,)-455.3 (B.,)-455.3 (Baylin,)-455.3 (S.B.,)-455.3 (and)-455.3 (Schuebel,)-455.3 (K.E.)]TJ T* [(2000.)-247.5 (CpG)-247.5 (methylation)-247.5 (is)-247.5 (maintained)-247.5 (in)-247.5 (human)-247.5 (cancer)-247.5 (cells)]TJ T* [(lacking)-332.7 (DNMT1.)]TJ /T1_1 1 Tf 8.3316 0 Td (Nature)Tj /T1_2 1 Tf 3.6108 0 Td (404:)Tj /T1_0 1 Tf 2.2241 0 Td (1003)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1007.)Tj -15.6665 -1.25 Td [(Rideout,)-268.8 (I.W.,)-268.8 (Eggan,)-268.8 (K.,)-268.8 (and)-268.8 (Jaenisch,)-268.8 (R.)-268.8 (2001.)-268.8 (Nuclear)-268.8 (cloning)]TJ 33.75 81.25 Td [(and)-746.1 (epigenetic)-746.1 (reprogramming)-746.1 (of)-746.1 (the)-746.1 (genome.)]TJ /T1_1 1 Tf 24.2549 0 Td (Science)Tj /T1_2 1 Tf -24.2549 -1.25 Td (293:)Tj /T1_0 1 Tf 2.2241 0 Td (1093)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1098.)Tj -3.7241 -1.25 Td [(Riggs,)-672.2 (A.D.)-672.2 (1975.)-672.2 (X-inactivation,)-672.2 (differentiation)-672.2 (and)-672.2 (DNA)]TJ 1.5 -1.25 Td (methylation.)Tj /T1_1 1 Tf 6.3328 0 Td [(Cytogenet.)-332.7 (Cell.)-332.7 (Genet.)]TJ /T1_2 1 Tf 11.3884 0 Td (14:)Tj /T1_0 1 Tf 1.6681 0 Td (9)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (25.)Tj -20.8893 -1.25 Td [(Riggs,)-364 (A.D.,)-364 (Xiong,)-364 (Z.,)-364 (Wang,)-364 (L.,)-364 (and)-364 (LeBon,)-364 (J.M.)-364 (1998.)-364 (Meth-)]TJ 1.5 -1.25 Td [(ylation)-552.2 (dynamics,)-552.2 (epigenetic)-552.2 (fidelity)-552.2 (and)-552.2 (X)-552.2 (chromosome)]TJ T* (structure.)Tj /T1_1 1 Tf 4.8328 0 Td [(Novartis)-332.7 (Found.)-332.7 (Symp.)]TJ /T1_2 1 Tf 11.1674 0 Td (214:)Tj /T1_0 1 Tf 2.2241 0 Td (214)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (225.)Tj -19.7243 -1.25 Td [(Robertson,)-344.1 (K.D.,)-344.1 (Ait-Si-Ali,)-344.1 (S.,)-344.1 (Yokochi,)-344.1 (T.,)-344.1 (Wade,)-344.1 (P.A.,)-344.1 (Jones,)]TJ 1.5 -1.25 Td [(P.L.,)-330.6 (and)-330.6 (Wolffe,)-330.6 (A.P.)-330.6 (2000.)-330.6 (DNMT1)-330.6 (forms)-330.6 (a)-330.6 (complex)-330.6 (with)]TJ T* [(Rb,)-295.8 (E2F1)-295.8 (and)-295.8 (HDAC1)-295.8 (and)-295.8 (represses)-295.8 (transcription)-295.8 (from)-295.8 (E2F-)]TJ T* [(responsive)-332.7 (promoters.)]TJ /T1_1 1 Tf 10.5556 0 Td [(Nat.)-332.7 (Genet.)]TJ /T1_2 1 Tf 5.8326 0 Td (25:)Tj /T1_0 1 Tf 1.6681 0 Td (338)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (342.)Tj -19.5563 -1.25 Td [(Rougier,)-260.7 (N.,)-260.7 (Bourc)]TJ /T1_3 1 Tf (\222)Tj /T1_0 1 Tf [(his,)-260.7 (D.,)-260.7 (Gomes,)-260.7 (D.M.,)-260.7 (Niveleau,)-260.7 (A.,)-260.7 (Plachot,)]TJ 1.5 -1.25 Td [(M.,)-377.1 (Paldi,)-377.1 (A.,)-377.1 (and)-377.1 (Viegas-Pequignot,)-377.1 (E.)-377.1 (1998.)-377.1 (Chromosome)]TJ T* [(methylation)-536.9 (patterns)-536.9 (during)-536.9 (mammalian)-536.9 (preimplantation)]TJ T* (development.)Tj /T1_1 1 Tf 6.6118 0 Td (Genes)Tj /T1_0 1 Tf 3.2208 0 Td (&)Tj /T1_1 1 Tf 1.2218 0 Td (Dev.)Tj /T1_2 1 Tf 2.4998 0 Td (12:)Tj /T1_0 1 Tf 1.6681 0 Td (2108)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2113.)Tj -16.7223 -1.25 Td [(Russo,)-337.4 (V.E.A.,)-337.4 (Martienssen,)-337.4 (R.A.,)-337.4 (and)-337.4 (Riggs,)-337.4 (A.D.)-337.4 (1996.)]TJ /T1_1 1 Tf 26.4232 0 Td (Epige-)Tj -24.9232 -1.25 Td [(netic)-441.4 (mechanisms)-441.4 (of)-441.4 (gene)-441.4 (regulation.)]TJ /T1_0 1 Tf 18.4833 0 Td [(Cold)-441.4 (Spring)-441.4 (Harbor)]TJ -18.4833 -1.25 Td [(Laboratory)-332.8 (Press,)-332.7 (Cold)-332.7 (Spring)-332.8 (Harbor,)-332.7 (NY.)]TJ -1.5 -1.25 Td [(Sado,)-275.2 (T.,)-275.2 (Fenner,)-275.2 (M.H.,)-275.2 (Tan,)-275.2 (S.S.,)-275.2 (Tam,)-275.2 (P.,)-275.2 (Shioda,)-275.2 (T.,)-275.2 (and)-275.2 (Li,)-275.2 (E.)]TJ 1.5 -1.25 Td [(2000.)-573.5 (X)-573.5 (inactivation)-573.5 (in)-573.5 (the)-573.5 (mouse)-573.5 (embryo)-573.5 (deficient)-573.5 (for)]TJ T* [(Dnmt1:)-515.3 (Distinct)-515.3 (effect)-515.3 (of)-515.3 (hypomethylation)-515.3 (on)-515.3 (imprinted)]TJ T* [(and)-332.8 (random)-332.8 (X)-332.8 (inactivation.)]TJ /T1_1 1 Tf 13.1651 0 Td [(Dev.)-332.7 (Biol.)]TJ /T1_2 1 Tf 4.9995 0 Td (225:)Tj /T1_0 1 Tf 2.2241 0 Td (294)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (303.)Tj -21.8888 -1.25 Td [(Selker,)-337.7 (E.U.)-337.7 (1990.)-337.7 (DNA)-337.7 (methylation)-337.7 (and)-337.7 (chromatin)-337.7 (structure:)]TJ 1.5 -1.25 Td [(A)-332.8 (view)-332.8 (from)-332.8 (below.)]TJ /T1_1 1 Tf 9.6091 0 Td [(Trends)-332.7 (Biochem.)-332.7 (Sci.)]TJ /T1_2 1 Tf 10.2764 0 Td (15:)Tj /T1_0 1 Tf 1.6681 0 Td (103)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (107.)Tj /T1_3 1 Tf -23.0536 -1.25 Td (\227\227\227)Tj /T1_0 1 Tf [(.)-295.5 (1999.)-295.5 (Gene)-295.5 (silencing:)-295.5 (Repeats)-295.5 (that)-295.5 (count.)]TJ /T1_1 1 Tf 23.1805 0 Td (Cell)Tj /T1_2 1 Tf 2.2395 0 Td (97:)Tj /T1_0 1 Tf 1.6681 0 Td (157)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf -25.5881 -1.25 Td (160.)Tj -1.5 -1.25 Td [(Shemer,)-323.5 (R.,)-323.5 (Hershko,)-323.5 (A.Y.,)-323.5 (Perk,)-323.5 (J.,)-323.5 (Mostoslavsky,)-323.5 (R.,)-323.5 (Tsuberi,)]TJ 1.5 -1.25 Td [(B.,)-225.1 (Cedar,)-225.1 (H.,)-225.1 (Buiting,)-225.2 (K.,)-225.1 (and)-225.1 (Razin,)-225.1 (A.)-225.1 (2000.)-225.1 (The)-225.1 (imprinting)]TJ T* [(box)-422.2 (of)-422.2 (the)-422.2 (Prader-Willi/Angelman)-422.2 (syndrome)-422.2 (domain.)]TJ /T1_1 1 Tf 25.7007 0 Td (Nat.)Tj -25.7007 -1.25 Td (Genet.)Tj /T1_2 1 Tf 3.4438 0 Td (26:)Tj /T1_0 1 Tf 1.6681 0 Td (440)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (443.)Tj -6.6119 -1.25 Td [(Siegfried,)-305.8 (Z.,)-305.8 (Eden,)-305.8 (S.,)-305.8 (Mendelsohn,)-305.8 (M.,)-305.8 (Feng,)-305.8 (X.,)-305.8 (Tsuberi,)-305.8 (B.Z.,)]TJ 1.5 -1.25 Td [(and)-377.5 (Cedar,)-377.5 (H.)-377.5 (1999.)-377.5 (DNA)-377.5 (methylation)-377.5 (represses)-377.5 (transcrip-)]TJ T* [(tion)-332.7 (in)-332.8 (vivo.)]TJ /T1_1 1 Tf 6.1103 0 Td [(Nat.)-332.7 (Genet.)]TJ /T1_2 1 Tf 5.8326 0 Td (22:)Tj /T1_0 1 Tf 1.6681 0 Td (203)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (206.)Tj -15.111 -1.25 Td [(Silva,)-247.5 (A.J.,)-247.5 (Ward,)-247.5 (K.,)-247.5 (and)-247.5 (White,)-247.5 (R.)-247.5 (1993.)-247.5 (Mosaic)-247.5 (methylation)-247.5 (in)]TJ 1.5 -1.25 Td [(clonal)-332.7 (tissue.)]TJ /T1_1 1 Tf 6.4976 0 Td [(Dev.)-332.7 (Biol.)]TJ /T1_2 1 Tf 4.9995 0 Td (156:)Tj /T1_0 1 Tf 2.2241 0 Td (391)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (398.)Tj -15.2212 -1.25 Td [(Simmen,)-406.6 (M.W.,)-406.6 (Leitgeb,)-406.6 (S.,)-406.6 (Charlton,)-406.6 (J.,)-406.6 (Jones,)-406.6 (S.J.M.,)-406.6 (Harris,)]TJ 1.5 -1.25 Td [(B.R.,)-364.7 (Clark,)-364.7 (V.H.,)-364.7 (and)-364.7 (Bird,)-364.7 (A.)-364.7 (1999.)-364.7 (Nonmethylated)-364.7 (trans-)]TJ T* [(posable)-476.2 (elements)-476.2 (and)-476.2 (methylated)-476.2 (genes)-476.2 (in)-476.2 (a)-476.2 (chordate)-476.2 (ge-)]TJ T* (nome.)Tj /T1_1 1 Tf 3.2218 0 Td (Science)Tj /T1_2 1 Tf 3.8328 0 Td (283:)Tj /T1_0 1 Tf 2.2241 0 Td (1164)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1167.)Tj -10.7787 -1.25 Td [(Smit,)-448.2 (A.F.)-448.2 (1999.)-448.2 (Interspersed)-448.2 (repeats)-448.2 (and)-448.2 (other)-448.2 (mementos)-448.2 (of)]TJ 1.5 -1.25 Td [(transposable)-293 (elements)-293 (in)-293 (mammalian)-293 (genomes.)]TJ /T1_1 1 Tf 22.3502 0 Td [(Curr.)-293 (Opin.)]TJ -22.3502 -1.25 Td [(Genet.)-332.7 (Dev.)]TJ /T1_2 1 Tf 5.9436 0 Td (9:)Tj /T1_0 1 Tf 1.1121 0 Td (657)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (663.)Tj -8.5557 -1.25 Td [(Smith,)-324.2 (S.S.,)-324.2 (Kan,)-324.2 (J.L.C.,)-324.2 (Baker,)-324.2 (D.J.,)-324.2 (Kaplan,)-324.2 (B.E.,)-324.2 (and)-324.2 (Dembek,)]TJ 1.5 -1.25 Td [(P.)-323.5 (1991.)-323.5 (Recognition)-323.5 (of)-323.5 (unusual)-323.5 (DNA)-323.5 (structures)-323.5 (by)-323.5 (human)]TJ T* (DNA\(cytosine-5\)methyltransferase.)Tj /T1_1 1 Tf 16.7436 0 Td [(J.)-299.4 (Mol.)-299.4 (Biol.)]TJ /T1_2 1 Tf 5.7872 0 Td (217:)Tj /T1_0 1 Tf 2.2241 0 Td (39)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (51.)Tj -26.2549 -1.25 Td [(Stancheva,)-469.1 (I.)-469.1 (and)-469.1 (Meehan,)-469.1 (R.R.)-469.1 (2000.)-469.1 (Transient)-469.1 (depletion)-469.1 (of)]TJ 1.5 -1.25 Td [(xDnmt1)-289.1 (leads)-289.1 (to)-289.1 (premature)-289.1 (gene)-289.1 (activation)-289.1 (in)]TJ /T1_1 1 Tf 21.6907 0 Td (Xenopus)Tj /T1_0 1 Tf 4.2891 0 Td (em-)Tj -25.9799 -1.25 Td (bryos.)Tj /T1_1 1 Tf 3.1118 0 Td (Genes)Tj /T1_0 1 Tf 3.2208 0 Td (&)Tj /T1_1 1 Tf 1.2218 0 Td (Dev.)Tj /T1_2 1 Tf 2.4998 0 Td (14:)Tj /T1_0 1 Tf 1.6681 0 Td (313)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (327.)Tj -13.2222 -1.25 Td [(Stewart,)-274.9 (C.L.,)-274.9 (Stuhlmann,)-274.9 (H.,)-274.9 (Jahner,)-274.9 (D.,)-274.9 (and)-274.9 (Jaenisch,)-274.9 (R.)-274.9 (1982.)]TJ 1.5 -1.25 Td [(De)-377.8 (novo)-377.9 (methylation)-377.8 (and)-377.8 (infectivity)-377.8 (of)-377.8 (retroviral)-377.9 (genomes)]TJ T* [(introduced)-663 (into)-663 (embryonal)-663 (carcinoma)-663 (cells.)]TJ /T1_1 1 Tf 22.3713 0 Td [(Proc.)-663 (Natl.)]TJ -22.3713 -1.25 Td [(Acad.)-332.7 (Sci.)]TJ /T1_2 1 Tf 5.0555 0 Td (79:)Tj /T1_0 1 Tf 1.6681 0 Td (4098)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (4102.)Tj -8.2237 -1.25 Td (St)Tj /T1_3 1 Tf (\366)Tj /T1_0 1 Tf [(ger,)-317.8 (R.,)-317.8 (Kajimura,)-317.8 (T.M.,)-317.8 (Brown,)-317.8 (W.T.,)-317.8 (and)-317.8 (Laird,)-317.8 (C.D.)-317.8 (1997.)]TJ 1.5 -1.25 Td [(Epigenetic)-478 (variation)-478 (illustrated)-478 (by)-478 (DNA)-478 (methylation)-478 (pat-)]TJ T* [(terns)-343 (of)-343 (the)-343 (fragile-X)-343.1 (gene)]TJ /T1_1 1 Tf 12.4914 0 Td (FMR1)Tj /T1_0 1 Tf (.)Tj /T1_1 1 Tf 3.399 0 Td [(Hum.)-343 (Mol.)-343 (Gen.)]TJ /T1_2 1 Tf 8.0282 0 Td (6:)Tj /T1_0 1 Tf 1.1121 0 Td (1791)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf -25.0308 -1.25 Td (1801.)Tj -1.5 -1.25 Td [(Swisher,)-513.9 (J.F.,)-513.9 (Rand,)-513.9 (E.,)-513.9 (Cedar,)-513.9 (H.,)-513.9 (and)-513.9 (Marie)-513.9 (Pyle,)-513.9 (A.)-513.9 (1998.)]TJ 1.5 -1.25 Td [(Analysis)-283 (of)-283 (putative)-283 (RNase)-283 (sensitivity)-283 (and)-283 (protease)-283 (insensi-)]TJ T* [(tivity)-434.7 (of)-434.7 (demethylation)-434.7 (activity)-434.7 (in)-434.7 (extracts)-434.7 (from)-434.7 (rat)-434.7 (myo-)]TJ T* (blasts.)Tj /T1_1 1 Tf 3.2768 0 Td [(Nucleic)-332.7 (Acids)-332.7 (Res.)]TJ /T1_2 1 Tf 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>> stream BT /GS0 gs /T1_0 1 Tf 7.9824 0 0 7.9824 87.5424 727.3275 Tm [(ming)-306.1 (of)-306.1 (somatic)-306.1 (nucleus)-306.1 (in)-306.1 (hybrid)-306.1 (cells.)]TJ /T1_1 1 Tf 19.029 0 Td [(EMBO)-306.1 (J.)]TJ /T1_2 1 Tf 4.3343 0 Td (16:)Tj /T1_0 1 Tf 1.6681 0 Td (6510)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf -25.0314 -1.25 Td (6520.)Tj -1.5 -1.25 Td [(Tamaru,)-361.5 (H.)-361.5 (and)-361.5 (Selker,)-361.5 (E.U.)-361.5 (2001.)-361.5 (A)-361.5 (histone)-361.5 (H3)-361.5 (methyltrans-)]TJ 1.5 -1.25 Td [(ferase)-616.8 (controls)-616.8 (DNA)-616.8 (methylation)-616.8 (in)-616.8 (Neurospora)-616.8 (crassa.)]TJ /T1_1 1 Tf 0 -1.25 TD (Nature)Tj /T1_2 1 Tf 3.6108 0 Td (414:)Tj /T1_0 1 Tf 2.2241 0 Td (277)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (283.)Tj -7.3349 -1.25 Td [(Tazi,)-410.9 (J.)-410.9 (and)-410.9 (Bird,)-410.9 (A.)-410.9 (1990.)-410.9 (Alternative)-410.9 (chromatin)-410.9 (structure)-410.9 (at)]TJ 1.5 -1.25 Td [(CpG)-332.8 (islands.)]TJ /T1_1 1 Tf 6.3316 0 Td (Cell)Tj /T1_2 1 Tf 2.2768 0 Td (60:)Tj /T1_0 1 Tf 1.6681 0 Td (909)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (920.)Tj -11.7764 -1.25 Td [(Thomassin,)-299.7 (H.,)-299.7 (Flavin,)-299.7 (M.,)-299.7 (Espinas,)-299.7 (M.L.,)-299.7 (and)-299.7 (Grange,)-299.7 (T.)-299.7 (2001.)]TJ 1.5 -1.25 Td [(Glucocorticoid-induced)-938.9 (DNA)-938.9 (demethylation)-938.9 (and)-938.9 (gene)]TJ T* [(memory)-332.8 (during)-332.8 (development.)]TJ /T1_1 1 Tf 14.1664 0 Td [(EMBO)-332.8 (J.)]TJ /T1_2 1 Tf 4.3875 0 Td (20:)Tj /T1_0 1 Tf 1.6681 0 Td (1974)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1983.)Tj -21.7221 -1.25 Td [(Tremblay,)-373.6 (K.D.,)-373.6 (Duran,)-373.6 (K.L.,)-373.6 (and)-373.6 (Bartolomei,)-373.6 (M.S.)-373.6 (1997.)-373.6 (A)-373.6 (5)]TJ /T1_4 1 Tf [-0.2 (\001)]TJ /T1_0 1 Tf 1.5 -1.25 Td [(2-kilobase-pair)-316.8 (region)-316.8 (of)-316.8 (the)-316.8 (imprinted)-316.8 (mouse)-316.8 (H19)-316.8 (gene)-316.8 (ex-)]TJ T* [(hibits)-429.3 (exclusive)-429.3 (paternal)-429.3 (methylation)-429.3 (throughout)-429.3 (develop-)]TJ T* (ment.)Tj /T1_1 1 Tf 3.0548 0 Td [(Mol.)-332.7 (Cell.)-332.7 (Biol.)]TJ /T1_2 1 Tf 7.4983 0 Td (17:)Tj /T1_0 1 Tf 1.6681 0 Td (4322)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (4329.)Tj -13.7212 -1.25 Td [(Turker,)-599.8 (M.S.)-599.8 (1999.)-599.8 (The)-599.8 (establishment)-599.8 (and)-599.8 (maintenance)-599.8 (of)]TJ 1.5 -1.25 Td [(DNA)-354.4 (methylation)-354.4 (patterns)-354.4 (in)-354.4 (mouse)-354.4 (somatic)-354.4 (cells.)]TJ /T1_1 1 Tf 24.5342 0 Td (Semin.)Tj -24.5342 -1.25 Td [(Cancer)-332.7 (Biol.)]TJ /T1_2 1 Tf 6.1666 0 Td (9:)Tj /T1_0 1 Tf 1.1121 0 Td (329)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (337.)Tj -8.7787 -1.25 Td [(Tweedie,)-330.6 (S.,)-330.6 (Charlton,)-330.6 (J.,)-330.6 (Clark,)-330.6 (V.,)-330.6 (and)-330.6 (Bird,)-330.6 (A.)-330.6 (1997.)-330.6 (Methyl-)]TJ 1.5 -1.25 Td [(ation)-432.9 (of)-432.9 (genomes)-432.9 (and)-432.9 (genes)-432.9 (at)-432.9 (the)-432.9 (invertebrate)]TJ /T1_3 1 Tf [-0.2 (\226)]TJ /T1_0 1 Tf (vertebrate)Tj T* (boundary.)Tj /T1_1 1 Tf 4.9458 0 Td [(Mol.)-332.7 (Cell.)-332.7 (Biol.)]TJ /T1_2 1 Tf 7.4983 0 Td (17:)Tj /T1_0 1 Tf 1.6681 0 Td (1469)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1475.)Tj -15.6123 -1.25 Td [(Tweedie,)-219.5 (S.,)-219.5 (Ng,)-219.5 (H.-H.,)-219.5 (Barlow,)-219.5 (A.L.,)-219.5 (Turner,)-219.5 (B.M.,)-219.5 (Hendrich,)-219.5 (B.,)]TJ 1.5 -1.25 Td [(and)-269.9 (Bird,)-269.9 (A.)-269.9 (1999.)-269.9 (Vestiges)-269.9 (of)-269.9 (a)-269.9 (DNA)-269.9 (methylation)-269.9 (system)-269.9 (in)]TJ /T1_1 1 Tf T* [(Drosophila)-332.8 (melanogaster)]TJ /T1_0 1 Tf [-0.1 (.)]TJ /T1_1 1 Tf 12.3886 0 Td [(Nat.)-332.7 (Genet.)]TJ /T1_2 1 Tf 5.8326 0 Td (23:)Tj /T1_0 1 Tf 1.6681 0 Td (389)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (390.)Tj -21.3893 -1.25 Td [(Um,)-419.4 (S.,)-419.4 (Harbers,)-419.4 (M.,)-419.4 (Benecke,)-419.4 (A.,)-419.4 (Pierrat,)-419.4 (B.,)-419.4 (Losson,)-419.4 (R.,)-419.4 (and)]TJ 1.5 -1.25 Td [(Chambon,)-432.9 (P.)-432.9 (1998.)-432.9 (Retinoic)-432.9 (acid)-432.9 (receptors)-432.9 (interact)-432.9 (physi-)]TJ T* [(cally)-331 (and)-331 (functionally)-331 (with)-331 (the)-331 (T:G)-331 (mismatch-specific)-331 (thy-)]TJ T* [(mine-DNA)-332.8 (glycosylase.)]TJ /T1_1 1 Tf 11.3866 0 Td [(J.)-332.7 (Biol.)-332.7 (Chem.)]TJ /T1_2 1 Tf 6.8873 0 Td (273:)Tj /T1_0 1 Tf 2.2241 0 Td (20728)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (20736.)Tj -21.9981 -1.25 Td [(Venolia,)-267.8 (L.,)-267.8 (Gartler,)-267.8 (S.M.,)-267.8 (Wasserman,)-267.8 (E.R.,)-267.8 (Yen,)-267.8 (P.,)-267.8 (Mohandas,)]TJ 1.5 -1.25 Td [(T.,)-256.8 (and)-256.8 (Shapiro,)-256.8 (L.J.)-256.8 (1982.)-256.8 (Transformation)-256.8 (with)-256.8 (DNA)-256.8 (from)-256.8 (5)]TJ T* [(azacytidine-reactivated)-428.6 (X)-428.6 (chromosomes.)]TJ /T1_1 1 Tf 19.4531 0 Td [(Proc.)-428.6 (Natl.)-428.6 (Acad.)]TJ -19.4531 -1.25 Td (Sci.)Tj /T1_2 1 Tf 1.9998 0 Td (79:)Tj /T1_0 1 Tf 1.6681 0 Td (2352)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2354.)Tj -5.1679 -1.25 Td [(Venter,)-385.7 (J.C.,)-385.7 (Adams,)-385.7 (M.D.,)-385.7 (Myers,)-385.7 (E.W.,)-385.7 (Li,)-385.7 (P.W.,)-385.7 (Mural,)-385.7 (R.J.,)]TJ 1.5 -1.25 Td [(Sutton,)-385.7 (G.G.,)-385.7 (Smith,)-385.7 (H.O.,)-385.7 (Yandell,)-385.7 (M.,)-385.7 (Evans,)-385.7 (C.A.,)-385.7 (Holt,)]TJ T* [(R.A.,)-358.7 (et)-358.7 (al.)-358.7 (2001.)-358.7 (The)-358.7 (sequence)-358.7 (of)-358.7 (the)-358.7 (human)-358.7 (genome.)]TJ /T1_1 1 Tf 26.033 0 Td (Sci-)Tj -26.033 -1.25 Td (ence)Tj /T1_2 1 Tf 2.4438 0 Td (291:)Tj /T1_0 1 Tf 2.2241 0 Td (1304)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (1351.)Tj -6.1679 -1.25 Td [(Viegas-Pequignot,)-370 (E.)-370 (and)-370 (Dutrillaux,)-370 (B.)-370 (1976.)-370 (Segmentation)-370 (of)]TJ 1.5 -1.25 Td [(human)-617.6 (chromosomes)-617.5 (induced)-617.5 (by)-617.5 (5-ACR)-617.5 (\(5-azacytidine\).)]TJ /T1_1 1 Tf T* [(Hum.)-332.7 (Genet.)]TJ /T1_2 1 Tf 6.4426 0 Td (34:)Tj /T1_0 1 Tf 1.6681 0 Td (247)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (254.)Tj -9.6107 -1.25 Td [(Voo,)-225.5 (K.S.,)-225.5 (Carlone,)-225.5 (D.L.,)-225.5 (Jacobsen,)-225.5 (B.M.,)-225.5 (Flodin,)-225.5 (A.,)-225.5 (and)-225.5 (Skalnik,)]TJ 1.5 -1.25 Td [(D.G.)-338.4 (2000.)-338.4 (Cloning)-338.4 (of)-338.4 (a)-338.4 (mammalian)-338.4 (transcriptional)-338.4 (activa-)]TJ T* [(tor)-256.8 (that)-256.8 (binds)-256.8 (unmethylated)-256.8 (CpG)-256.8 (motifs)-256.8 (and)-256.8 (shares)-256.8 (a)-256.8 (CXXC)]TJ T* [(domain)-274.5 (with)-274.5 (DNA)-274.5 (methyltransferase,)-274.5 (human)-274.5 (trithorax,)-274.5 (and)]TJ T* [(methyl-CpG)-608 (binding)-608 (domain)-608 (protein)-608 (1.)]TJ /T1_1 1 Tf 20.041 0 Td [(Mol.)-608 (Cell.)-608 (Biol.)]TJ /T1_2 1 Tf -20.041 -1.25 Td (20:)Tj /T1_0 1 Tf 1.6681 0 Td (2108)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (2121.)Tj -3.1681 -1.25 Td [(Wakayama,)-330.6 (T.)-330.6 (and)-330.6 (Yanagimachi,)-330.6 (R.)-330.6 (2001.)-330.6 (Mouse)-330.6 (cloning)-330.6 (with)]TJ 1.5 -1.25 Td [(nucleus)-373.9 (donor)-373.9 (cells)-373.9 (of)-373.9 (different)-373.9 (age)-373.9 (and)-373.9 (type.)]TJ /T1_1 1 Tf 21.6588 0 Td [(Mol.)-373.9 (Reprod.)]TJ -21.6588 -1.25 Td (Dev.)Tj /T1_2 1 Tf 2.4998 0 Td (58:)Tj /T1_0 1 Tf 1.6681 0 Td (376)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (383.)Tj -5.6679 -1.25 Td [(Walsh,)-392.8 (C.P.)-392.8 (and)-392.8 (Bestor,)-392.8 (T.H.)-392.8 (1999.)-392.8 (Cytosine)-392.8 (methylation)-392.8 (and)]TJ 1.5 -1.25 Td [(mammalian)-332.8 (development.)]TJ /T1_1 1 Tf 12.5537 0 Td (Genes)Tj /T1_0 1 Tf 3.2208 0 Td (&)Tj /T1_1 1 Tf 1.2218 0 Td (Dev.)Tj /T1_2 1 Tf 2.4998 0 Td (13:)Tj /T1_0 1 Tf 1.6681 0 Td (26)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (34.)Tj -22.6641 -1.25 Td [(Walsh,)-267.8 (C.P.,)-267.8 (Chaillet,)-267.8 (J.R.,)-267.8 (and)-267.8 (Bestor,)-267.8 (T.H.)-267.8 (1998.)-267.8 (Transcription)]TJ 1.5 -1.25 Td [(of)-433.2 (IAP)-433.2 (endogenous)-433.2 (retroviruses)-433.2 (is)-433.2 (constrained)-433.3 (by)-433.2 (cytosine)]TJ T* (methylation.)Tj /T1_1 1 Tf 6.3328 0 Td [(Nat.)-332.7 (Genet.)]TJ /T1_2 1 Tf 5.8326 0 Td (20:)Tj /T1_0 1 Tf 1.6681 0 Td (116)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (117.)Tj -15.3335 -1.25 Td [(Wang,)-224.4 (J.,)-224.4 (Mager,)-224.4 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(\222)Tj /T1_0 1 Tf [(Neill,)-434.7 (R.J.,)-434.7 (O)]TJ /T1_3 1 Tf (\222)Tj /T1_0 1 Tf [(Neill,)-434.7 (M.J.,)-434.7 (and)-434.7 (Marshall)-434.7 (Graves,)-434.7 (J.A.)]TJ 1.5 -1.25 Td [(1998.)-340.2 (Undermethylation)-340.2 (associated)-340.2 (with)-340.2 (retroelement)-340.2 (acti-)]TJ T* [(vation)-635.7 (and)-635.7 (chromosome)-635.7 (remodelling)-635.7 (in)-635.7 (an)-635.7 (interspecific)]TJ T* [(mammalian)-332.8 (hybrid.)]TJ /T1_1 1 Tf 9.5536 0 Td (Nature)Tj /T1_2 1 Tf 3.6108 0 Td (393:)Tj /T1_0 1 Tf 2.2241 0 Td (68)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf (72.)Tj -16.8885 -1.25 Td [(Weiss,)-376.4 (A.,)-376.4 (Keshet,)-376.4 (I.,)-376.4 (Razin,)-376.4 (A.,)-376.4 (and)-376.4 (Cedar,)-376.4 (H.)-376.4 (1996.)-376.4 (DNA)-376.4 (de-)]TJ 1.5 -1.25 Td [(methylation)-480.8 (in)-480.8 (vitro:)-480.8 (Involvement)-480.8 (of)-480.8 (RNA.)]TJ /T1_1 1 Tf 21.4972 0 Td (Cell)Tj /T1_2 1 Tf 2.4249 0 Td (86:)Tj /T1_0 1 Tf 1.6681 0 Td (709)Tj /T1_3 1 Tf (\226)Tj /T1_0 1 Tf -25.5902 -1.25 Td (718.)Tj 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