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Establishment and Maintenance of DNA Methylation Patterns in Mammals

  • Chapter
DNA Methylation: Basic Mechanisms

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 301))

Abstract

In mammals, CpG methylation patterns are established and maintained during development by the Dnmt1 and Dnmt3 families of DNA methyltransferases. These enzymes share conserved catalytic motifs in their C-terminal regions, but have unique N-terminal regulatory domains. Studies over the past several years have shed light on the molecular mechanisms by which DNA methylation patterns are regulated. This review focuses on recent advances in defining the functional domains of DNA methyltransferases and identifying interacting proteins that may contribute to the functional specializations of these enzymes.

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References

  • Aapola U, Lyle R, Krohn K, Antonarakis SE, Peterson P (2001) Isolation and initial characterization of the mouse Dnmt3 l gene. Cytogenet Cell Genet 92:122–126

    Article  CAS  PubMed  Google Scholar 

  • Aapola U, Liiv I, Peterson P (2002) Imprinting regulator DNMT3L is a transcriptional repressor associated with histone deacetylase activity. Nucleic Acids Res 30:3602–3608

    Article  CAS  PubMed  Google Scholar 

  • Aoki A, Suetake I, Miyagawa J, Fujio T, Chijiwa T, Sasaki H, Tajima S (2001) Enzymatic properties of de novo-type mouse DNA (cytosine-5) methyltransferases. Nucleic Acids Res 29:3506–3512

    Article  CAS  PubMed  Google Scholar 

  • Aoki K, Meng G, Suzuki K, Takashi T, Kameoka Y, Nakahara K, Ishida R, Kasai M (1998) RP58 associates with condensed chromatin and mediates a sequence-specific transcriptional repression. J Biol Chem 273:26698–26704

    Article  CAS  PubMed  Google Scholar 

  • Araujo FD, Croteau S, Slack AD, Milutinovic S, Bigey P, Price GB, Zannis-Hajopoulos M, Szyf M (2001) The DNMT1 target recognition domain resides in the N terminus. J Biol Chem 276:6930–6936

    Article  CAS  PubMed  Google Scholar 

  • Bachman KE, Rountree MR, Baylin SB (2001) Dnmt3a and Dnmt3b are transcriptional repressors that exhibit unique localization properties to heterochromatin. J Biol Chem 276:32282–32287

    Article  CAS  PubMed  Google Scholar 

  • Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410:120–124

    Article  CAS  PubMed  Google Scholar 

  • Beard C, Li E, Jaenisch R (1995) Loss of methylation activates Xist in somatic but not in embryonic cells. Genes Dev 9:2325–2334

    CAS  PubMed  Google Scholar 

  • Bestor T, Laudano A, Mattaliano R, Ingram V (1988) Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J Mol Biol 203:971–983

    Article  CAS  PubMed  Google Scholar 

  • Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21

    Article  CAS  PubMed  Google Scholar 

  • Bird AP, Wolffe AP (1999) Methylation-induced repression—belts, braces, and chromatin. Cell 99:451–454

    Article  CAS  PubMed  Google Scholar 

  • Bourc’his D, Bestor TH (2004) Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431:96–99

    CAS  PubMed  Google Scholar 

  • Bourc’his D, Xu GL, Lin CS, Bollman B, Bestor TH (2001) Dnmt3Landthe establishment of maternal genomic imprints. Science 294:2536–2539

    CAS  PubMed  Google Scholar 

  • Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T (1998) Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391:597–601

    CAS  PubMed  Google Scholar 

  • Brenner C, Deplus R, Didelot C, Loriot A, Vire E, De Smet C, Gutierrez A, Danovi D, Bernard D, Boon T, Pelicci PG, Amati B, Kouzarides T, de Launoit Y, Di Croce L, Fuks F (2005) Myc represses transcription through recruitment of DNA methyltransferase corepressor. EMBO J 24:336–346

    CAS  PubMed  Google Scholar 

  • Cameron EE, Bachman KE, Myohanen S, Herman JG, Baylin SB (1999) Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 21:103–107

    Article  CAS  PubMed  Google Scholar 

  • Chedin F, Lieber MR, Hsieh CL (2002) The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a. Proc Natl Acad Sci U S A 99:16916–16921

    Article  CAS  PubMed  Google Scholar 

  • Chen T, Li E (2004) Structure and function of eukaryotic DNA methyltransferases. Curr Top Dev Biol 60:55–89

    CAS  PubMed  Google Scholar 

  • Chen T, Ueda Y, Xie S, Li E (2002) A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation. J Biol Chem 277:38746–38754

    CAS  PubMed  Google Scholar 

  • Chen T, Ueda Y, Dodge JE, Wang Z, Li E (2003) Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b. Mol Cell Biol 23:5594–5605

    CAS  PubMed  Google Scholar 

  • Chen T, Tsujimoto N, Li E (2004) The PWWP domain of Dnmt3a and Dnmt3b is required for directing DNA methylation to the major satellite repeats at pericentric heterochromatin. Mol Cell Biol 24:9048–9058

    CAS  PubMed  Google Scholar 

  • Cheng X, Roberts RJ (2001) AdoMet-dependent methylation, DNA methyltransferases and base flipping. Nucleic Acids Res 29:3784–3795

    Article  CAS  PubMed  Google Scholar 

  • Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF (1997) Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target forp21WAF1. Science 277:1996–2000

    Article  CAS  PubMed  Google Scholar 

  • Deplus R, Brenner C, Burgers WA, Putmans P, Kouzarides T, de Launoit Y, Fuks F (2002) Dnmt3L is a transcriptional repressor that recruits histone deacetylase. Nucleic Acids Res 30:3831–3838

    Article  CAS  PubMed  Google Scholar 

  • Di Croce L, Raker VA, Corsaro M, Fazi F, Fanelli M, Faretta M, Fuks F, Lo Coco F, Kouzarides T, Nervi C, Minucci S, Pelicci PG (2002) Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science 295:1079–1082

    PubMed  Google Scholar 

  • Ding F, Chaillet JR (2002) In vivo stabilization of the Dnmt1 (cytosine-5)-methyltransferase protein. Proc Natl Acad Sci U S A 99:14861–14866

    CAS  PubMed  Google Scholar 

  • Dodge JE, Ramsahoye BH, Wo ZG, Okano M, Li E (2002) De novo methylation of MMLV provirus in embryonic stem cells: CpG versus non-CpG methylation. Gene 289:41–48

    Article  CAS  PubMed  Google Scholar 

  • Dodge JE, Okano M, Dick F, Tsujimoto N, Chen T, Wang S, Ueda Y, Dyson N, Li E (2005) Inactivation of Dnmt3b in mouse embryonic fibroblasts results in DNA hypomethylation, chromosomal instability, and spontaneous immortalization. J Biol Chem 280:17986–17991

    CAS  PubMed  Google Scholar 

  • Dong A, Yoder JA, Zhang X, Zhou L, Bestor TH, Cheng X (2001) Structure of human DNMT2, an enigmatic DNA methyltransferase homolog that displays denaturant-resistant binding to DNA. Nucleic Acids Res 29:439–448

    CAS  PubMed  Google Scholar 

  • Dunaief JL, Strober BE, Guha S, Khavari PA, Alin K, Luban J, Begemann M, Crabtree GR, Goff SP (1994) The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Cell 79:119–130

    Article  CAS  PubMed  Google Scholar 

  • Esteller M, Fraga MF, Paz MF, Campo E, Colomer D, Novo FJ, Calasanz MJ, Galm O, Guo M, Benitez J, Herman JG (2002) Cancer epigenetics and methylation. Science 297:1807–1808

    Article  PubMed  Google Scholar 

  • Fatemi M, Hermann A, Pradhan S, Jeltsch A (2001) The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA. J Mol Biol 309:1189–1199

    Article  CAS  PubMed  Google Scholar 

  • Feng Q, Zhang Y (2001) The MeCP1 complex represses transcription through preferential binding, remodeling, and deacetylating methylated nucleosomes. Genes Dev 15:827–832

    CAS  PubMed  Google Scholar 

  • Freitag M, Hickey PC, Khlafallah TK, Read ND, Selker EU (2004) HP1 is essential for DNA methylation in neurospora. Mol Cell 13:427–434

    Article  CAS  PubMed  Google Scholar 

  • Fuks F, Burgers WA, Brehm A, Hughes-Davies L, Kouzarides T (2000) DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat Genet 24:88–91

    CAS  PubMed  Google Scholar 

  • Fuks F, Burgers WA, Godin N, Kasai M, Kouzarides T (2001) Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription. EMBO J 20:2536–2544

    Article  CAS  PubMed  Google Scholar 

  • Fuks F, Hurd PJ, Deplus R, Kouzarides T (2003) The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res 31:2305–2312

    Article  CAS  PubMed  Google Scholar 

  • Ge Y-Z, Pu M-T, Gowher H, Wu H-P, Ding J-P, Jeltsch A, Xu G-L (2004) Chromatin targeting of de novo DNA methyltransferases by the PWWP domain. J Biol Chem 279:25447–25454

    CAS  PubMed  Google Scholar 

  • Gill G (2004) SUMO and ubiquitin in the nucleus: different functions, similar mechanisms? Genes Dev 18:2046–2059

    Article  CAS  PubMed  Google Scholar 

  • Gowher H, Liebert K, Hermann A, Xu G, Jeltsch A (2005) Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L. J Biol Chem 280:13341–13348

    Article  CAS  PubMed  Google Scholar 

  • Grignani F, De Matteis S, Nervi C, Tomassoni L, Gelmetti V, Cioce M, Fanelli M, Ruthardt M, Ferrara FF, Zamir I, Seiser C, Lazar MA, Minucci S, Pelicci PG (1998) Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Nature 391:815–818

    CAS  PubMed  Google Scholar 

  • Hata K, Okano M, Lei H, Li E (2002) Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development 129:1983–1993

    CAS  PubMed  Google Scholar 

  • Hendrich B, Bird A (1998) Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol 18:6538–6547

    CAS  PubMed  Google Scholar 

  • Hermann A, Schmitt S, Jeltsch A (2003) The human Dnmt2 has residual DNA-(cytosine-C5) methyltransferase activity. J Biol Chem 278:31717–31721

    Article  CAS  PubMed  Google Scholar 

  • Hsieh CL (1999) In vivo activity of murine de novo methyltransferases, Dnmt3a and Dnmt3b. Mol Cell Biol 19:8211–8218

    CAS  PubMed  Google Scholar 

  • Hung MS, Karthikeyan N, Huang B, Koo HC, Kiger J, Shen CJ (1999) Drosophila proteins related to vertebrate DNA (5-cytosine) methyltransferases. Proc Natl Acad Sci U S A 96:11940–11945

    CAS  PubMed  Google Scholar 

  • Iida T, Suetake I, Tajima S, Morioka H, Ohta S, Obuse C, Tsurimoto T (2002) PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimethylated DNA. Genes Cells 7:997–1007

    CAS  PubMed  Google Scholar 

  • Jackson JP, Lindroth AM, Cao X, Jacobsen SE (2002) Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature 416:556–560

    Article  CAS  PubMed  Google Scholar 

  • Jaenisch R (1997) DNA methylation and imprinting: why bother? Trends Genet 13:323–329

    Article  CAS  PubMed  Google Scholar 

  • Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33Suppl:245–254

    CAS  PubMed  Google Scholar 

  • Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J, Wolffe AP (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19:187–191

    Article  CAS  PubMed  Google Scholar 

  • Kaneda M, Okano M, Hata K, Sado T, Tsujimoto N, Li E, Sasaki H (2004) Essential role for denovo DNA methyltransferases Dnmt3a in paternal and maternal imprinting. Nature 429:900–903

    Article  CAS  PubMed  Google Scholar 

  • Kang ES, Park CW, Chung JH (2001) Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1. Biochem Biophys Res Commun 289:862–868

    Article  CAS  PubMed  Google Scholar 

  • Kimura H, Shiota K (2003) Methyl-CpG-binding protein, MeCP2, is a target molecule for maintenance DNA methyltransferase, Dnmt1. J Biol Chem 278:4806–4812

    CAS  PubMed  Google Scholar 

  • Kunert N, Marhold J, Stanke J, Stach D, Lyko F (2003) A Dnmt2-like protein mediates DNA methylation in Drosophila. Development 130:5083–5090

    Article  CAS  PubMed  Google Scholar 

  • Lachner M, O’Carroll D, Rea S, Mechtler K, Jenuwein T (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410:116–120

    Article  CAS  PubMed  Google Scholar 

  • Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E, Jenuwein T, Peters AH (2003) Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation tomajor satellite repeats at pericentric heterochromatin. Curr Biol 13:1192–1200

    Article  CAS  PubMed  Google Scholar 

  • Lei H, Oh SP, Okano M, Juttermann R, Goss KA, Jaenisch R, Li E (1996) De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development 122:3195–3205

    CAS  PubMed  Google Scholar 

  • Leonhardt H, Page AW, Weier H-U, Bestor TH (1992) A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 71:865–873

    Article  CAS  PubMed  Google Scholar 

  • Lewis JD, Meehan RR, Henzel WJ, Maurer-Fogy I, Jeppesen P, Klein F, Bird A (1992) Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 69:905–914

    Article  CAS  PubMed  Google Scholar 

  • Li E (2002) Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet 3:662–673

    Article  CAS  PubMed  Google Scholar 

  • Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–926

    CAS  PubMed  Google Scholar 

  • Li E, Beard C, Jaenisch R (1993) Role for DNA methylation in genomic imprinting. Nature 366:362–365

    CAS  PubMed  Google Scholar 

  • Liang G, Chan MF, Tomigahara Y, Tsai YC, Gonzales FA, Li E, Laird PW, Jones PA (2002) Cooperativity between DNA methyltransferases in the maintenance methylation of repetitive elements. Mol Cell Biol 22:480–491

    Article  CAS  PubMed  Google Scholar 

  • Lin RJ, Nagy L, Inoue S, Shao W, Miller WH Jr, Evans RM (1998) Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature 391:811–814

    CAS  PubMed  Google Scholar 

  • Ling Y, Sankpal UT, Robertson AK, McNally JG, Karpova T, Robertson KD (2004) Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription. Nucleic Acids Res 32:598–610

    Article  CAS  PubMed  Google Scholar 

  • Liu K, Wang YF, Cantemir C, Muller MT (2003) Endogenous assays of DNA methyltransferases: evidence for differential activities of DNMT1, DNMT2, and DNMT3 in mammalian cells in vivo. Mol Cell Biol 23:2709–2719

    CAS  PubMed  Google Scholar 

  • Liu Y, Oakeley EJ, Sun L, Jost JP (1998) Multiple domains are involved in the targeting of the mouse DNA methyltransferase to the DNA replication foci. Nucleic Acids Res 26:1038–1045

    CAS  PubMed  Google Scholar 

  • Liu Z, Fisher RA (2004) RGS6 interacts with DMAP1 and DNMT1 and inhibits DMAP1 transcriptional repressor activity. J Biol Chem 279:14120–14128

    CAS  PubMed  Google Scholar 

  • Luo RX, Postigo AA, Dean DC (1998) Rb interacts with histone deacetylase to repress transcription. Cell 92:463–473

    Article  CAS  PubMed  Google Scholar 

  • Lyko F, Ramsahoye BH, Kashevsky H, Tudor M, Mastrangelo MA, Orr-Weaver TL, Jaenisch R (1999) Mammalian (cytosine-5) methyltransferases cause genomic DNA methylation and lethality in Drosophila. Nat Genet 23:363–366

    CAS  PubMed  Google Scholar 

  • Lyko F, Whittaker AJ, Orr-Weaver TL, Jaenisch R (2000) The putative Drosophila methyltransferase gene dDnmt2 is contained in a transposon-like element and is expressed specifically in ovaries. Mech Dev 95:215–217

    Article  CAS  PubMed  Google Scholar 

  • Magnaghi-Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le Villain JP, Troalen F, Trouche D, Harel-Bellan A (1998) Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature 391:601–605

    CAS  PubMed  Google Scholar 

  • Malagnac F, Bartee L, Bender J (2002) An Arabidopsis SET domain protein required for maintenance but not establishment of DNA methylation. EMBO J 21:6842–6852

    Article  CAS  PubMed  Google Scholar 

  • Meehan RR, Lewis JD, McKay S, Kleiner EL, Bird AP (1989) Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs. Cell 58:499–507

    Article  CAS  PubMed  Google Scholar 

  • Muromoto R, Sugiyama K, Takachi A, Imoto S, Sato N, Yamamoto T, Oritani K, Shimoda K, Matsuda T (2004) Physical and functional interactions between Daxx and DNA methyltransferase 1-associated protein, DMAP1. J Immunol 172:2985–2993

    CAS  PubMed  Google Scholar 

  • Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393:386–389

    CAS  PubMed  Google Scholar 

  • Nielsen SJ, Schneider R, Bauer UM, Bannister AJ, Morrison A, O’Carroll D, Firestein R, Cleary M, Jenuwein T, Herrera RE, Kouzarides T (2001) Rb targets histone H3 methylation and HP1 to promoters. Nature 412:561–565

    Article  CAS  PubMed  Google Scholar 

  • Okano M, Xie S, Li E (1998a) Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 19:219–220

    CAS  PubMed  Google Scholar 

  • Okano M, Xie S, Li E (1998b) Dnmt2 is not required for de novo and maintenance methylation of viral DNA in embryonic stem cells. Nucleic Acids Res 26:2536–2540

    Article  CAS  PubMed  Google Scholar 

  • Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257

    Article  CAS  PubMed  Google Scholar 

  • Panning B, Jaenisch R (1996) DNA hypomethylation can activate Xist expression and silence X-linked genes. Genes Dev 10:1991–2002

    CAS  PubMed  Google Scholar 

  • Patel JH, Loboda AP, Showe MK, Showe LC, McMahon SB (2004) Analysis of genomic targets reveals complex functions of MYC. Nat Rev Cancer 4:562–568

    Article  CAS  PubMed  Google Scholar 

  • Pelengaris S, Khan M, Evan G (2002) c-MYC: more than just a matter of life and death. Nat Rev Cancer 2:764–776

    Article  CAS  PubMed  Google Scholar 

  • Peterson EJ, Bogler O, Taylor SM (2003) p53-mediated repression of DNA methyltransferase 1 expression by specific DNA binding. Cancer Res 63:6579–6582

    CAS  PubMed  Google Scholar 

  • Pinarbasi E, Elliott J, Hornby DP (1996) Activation of a yeast pseudo DNA methyltransferase by deletion of a single amino acid. J Mol Biol 257:804–813

    Article  CAS  PubMed  Google Scholar 

  • Pradhan S, Kim GD (2002) The retinoblastoma gene product interacts with maintenance human DNA (cytosine-5) methyltransferase and modulates its activity. EMBO J 21:779–788

    Article  CAS  PubMed  Google Scholar 

  • Pradhan S, Bacolla A, Wells RD, Roberts RJ (1999) Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. J Biol Chem 274:33002–33010

    Article  CAS  PubMed  Google Scholar 

  • Qiu C, Sawada K, Zhang X, Cheng X (2002) The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds. Nat Struct Biol 9:217–224

    CAS  PubMed  Google Scholar 

  • Reik W, Dean W, Walter J (2001) Epigenetic reprogramming in mammalian development. Science 293:1089–1093

    Article  CAS  PubMed  Google Scholar 

  • Rhee I, Jair KW, Yen RW, Lengauer C, Herman JG, Kinzler KW, Vogelstein B, Baylin SB, Schuebel KE (2000) CpG methylation is maintained in human cancer cells lacking DNMT1. Nature 404:1003–1007

    CAS  PubMed  Google Scholar 

  • Rhee I, Bachman KE, Park BH, Jair KW, Yen RW, Schuebel KE, Cui H, Feinberg AP, Lengauer C, Kinzler KW, Baylin SB, Vogelstein B (2002) DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 416:552–556

    Article  CAS  PubMed  Google Scholar 

  • Robert MF, Morin S, Beaulieu N, Gauthier F, Chute IC, Barsalou A, MacLeod AR (2003) DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat Genet 33:61–65

    Article  CAS  PubMed  Google Scholar 

  • Robertson KD, Ait-Si-Ali S, Yokochi T, Wade PA, Jones PL, Wolffe AP (2000) DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nat Genet 25:338–342

    CAS  PubMed  Google Scholar 

  • Rountree MR, Bachman KE, Baylin SB (2000) DNMT1 binds HDAC2 and a new corepressor, DMAP1, to form a complex at replication foci. Nat Genet 25:269–277

    Article  CAS  PubMed  Google Scholar 

  • Shirohzu H, Kubota T, Kumazawa A, Sado T, Chijiwa T, Inagaki K, Suetake I, Tajima S, Wakui K, Miki Y, Hayashi M, Fukushima Y, Sasaki H (2002) Three novel DNMT3B mutations in Japanese patients with ICF syndrome. Am J Med Genet 112:31–37

    Article  PubMed  Google Scholar 

  • Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, Moroy T, Bartek J, Massague J, Hanel F, Eilers M (2001) Repression of p15INK4b expression by Myc through association with Miz-1. Nat Cell Biol 3:392–399

    Article  CAS  PubMed  Google Scholar 

  • Stec I, Nagl SB, van Ommen GJ, den Dunnen JT (2000) The PWWP domain: a potential protein-protein interaction domain in nuclear proteins influencing differentiation? FEBS Lett 473:1–5

    Article  CAS  PubMed  Google Scholar 

  • Suetake I, Shinozaki F, Miyagawa J, Takeshima H, Tajima S (2004) DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b througha direct interaction. J Biol Chem 279:27816–27823

    Article  CAS  PubMed  Google Scholar 

  • Tamaru H, Selker EU(2001) A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414:277–283

    Article  CAS  PubMed  Google Scholar 

  • Tang LY, Reddy MN, Rasheva V, Lee TL, Lin MJ, Hung MS, Shen CK (2003) The eukaryotic DNMT2 genes encode a new class of cytosine-5 DNA methyltransferases. J Biol Chem 278:33613–33616

    CAS  PubMed  Google Scholar 

  • Tatematsu KI, Yamazaki T, Ishikawa F (2000) MBD2-MBD3 complex binds to hemimethylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase. Genes Cells 5:677–688

    Article  CAS  PubMed  Google Scholar 

  • Trouche D, Le Chalony C, Muchardt C, Yaniv M, Kouzarides T (1997) RB and hbrm cooperate to repress the activation functions of E2F1. Proc Natl Acad Sci U S A 94:11268–11273

    Article  CAS  PubMed  Google Scholar 

  • Tweedie S, Ng HH, Barlow AL, Turner BM, Hendrich B, Bird A (1999) Vestiges of aDNA methylation system in Drosophila melanogaster? Nat Genet 23:389–390

    CAS  PubMed  Google Scholar 

  • Van den Wyngaert I, Sprengel J, Kass SU, Luyten WH (1998) Cloning and analysis of a novel human putative DNA methyltransferase. FEBS Lett 426:283–289

    PubMed  Google Scholar 

  • Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, Wolffe AP (1999) Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nat Genet 23:62–66

    CAS  PubMed  Google Scholar 

  • Weinberg RA(1995) The retinoblastoma protein and cell cycle control. Cell 81:323–330

    Google Scholar 

  • Wilkinson CR, Bartlett R, Nurse P, Bird AP (1995) The fission yeast gene pmt1+ encodes a DNA methyltransferase homologue. Nucleic Acids Res 23:203–210

    CAS  PubMed  Google Scholar 

  • Wu S, Cetinkaya C, Munoz-Alonso MJ, von der Lehr N, Bahram F, Beuger V, Eilers M, Leon J, Larsson LG (2003) Myc represses differentiation-induced p21CIP1 expression via Miz-1-dependent interaction with the p21 core promoter. Oncogene 22:351–360

    CAS  PubMed  Google Scholar 

  • Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW, Okumura K, Li E (1999) Cloning, expression and chromosome locations of the human DNMT3 gene family. Gene 236:87–95

    Article  CAS  PubMed  Google Scholar 

  • Yoder JA, Bestor TH (1998) A candidate mammalian DNA methyltransferase related to pmt1p of fission yeast. Hum Mol Genet 7:279–284

    Article  CAS  PubMed  Google Scholar 

  • Yoder JA, Soman NS, Verdine GL, Bestor TH (1997) DNA (cytosine-5)-methyltransferases in mouse cells and tissues. Studies with a mechanism-based probe. J Mol Biol 270:385–395

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Epigenetics Program, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA

    T. Chen & E. Li

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  1. T. Chen
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  2. E. Li
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Editors and Affiliations

  1. Institut für Genetik, Universität zu Köln, Zülpicher Str. 47, 50674, Köln, Germany

    Walter Doerfler (Prof. Dr.) & Petra Böhm (Prof. Dr.) & 

  2. Institut für Klinische und Molekulare Virologie, Universität Erlangen, Schlossgarten 4, 91054, Erlangen, Germany

    Walter Doerfler (Prof. Dr.) (Prof. Dr.)

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© 2006 Springer-Verlag Berlin Heidelberg

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Chen, T., Li, E. (2006). Establishment and Maintenance of DNA Methylation Patterns in Mammals. In: Doerfler, W., Böhm, P. (eds) DNA Methylation: Basic Mechanisms. Current Topics in Microbiology and Immunology, vol 301. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-31390-7_6

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