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Regulatory Networks in Stem Cells pp 247–256Cite as

Epigenetic Signature of Embryonal Stem Cells: A DNA Methylation Perspective

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Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

Specific epigenetic features underpin the pluripotency of ES cells. ES cells have a unique DNA methylation signature, express high levels of DNA de novo methyltransferases, and, unlike somatic cells, are capable of methylating exogenously introduced DNA. At the same time, ES cells protect specific CpG dinucleotides from undergoing de novo methylation, a process that clearly mimics what occurs in the normal embryo. ES cells protect CpG island– as well as non-CpG island–promoters that direct expression of genes involved in stem cell identity from de novo methylation. These promoters are apparently protected by virtue of inherent common sequence elements through binding of transcription machinery related factors. These mechanisms are critical for setting up the correct genome methylation pattern, which is mostly stable in somatic cells. Genes that belong to a self-organizing network of transcription that prevents differentiation and promote proliferation and pluripotency, such as Oct-3/4 and Nanog, are silenced during differentiation by histone modification as well as by DNA methylation. Indeed, genetic experiments have supported the notion that histone modification directs DNA methylation, which represents a second-line epigenetic change, the role of which is to permanently silence gene expression, thereby preventing reprogramming.

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References

  1. Bird A. DNA methylation patterns and epigenetic memory. Gene Dev. 2002;16(1):6–21.

    PubMed  CAS  Google Scholar 

  2. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693–705.

    PubMed  CAS  Google Scholar 

  3. Narlikar GJ, Fan HY, Kingston RE. Cooperation between complexes that regulate chromatin structure and transcription. Cell. 2002;108(4):475–87.

    PubMed  CAS  Google Scholar 

  4. Struhl K. Histone acetylation and transcriptional regulatory mechanisms. Genes Dev. 1998;12(5):599–606.

    PubMed  CAS  Google Scholar 

  5. Santos-Rosa H, Schneider R, Bannister AJ, et al. Active genes are tri-methylated at K4 of histone H3. Nature. 2002;419(6905): 407–11.

    PubMed  CAS  Google Scholar 

  6. Nakayama J, Rice JC, Strahl BD, Allis CD, Grewal SI. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science. 2001;292(5514):110–3.

    PubMed  CAS  Google Scholar 

  7. Plath K, Fang J, Mlynarczyk-Evans SK, et al. Role of histone H3 lysine 27 methylation in X inactivation. Science . 2003;300(5616):131–5.

    PubMed  CAS  Google Scholar 

  8. Koyanagi M, Baguet A, Martens J, Margueron R, Jenuwein T, Bix M. EZH2 and histone 3 trimethyl lysine 27 associated with Il4 and Il13 gene silencing in Th1 cells. J Biol Chem. 2005;280(36):31470–7.

    PubMed  CAS  Google Scholar 

  9. Li E. Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev. 2002;3(9):662–73.

    CAS  Google Scholar 

  10. Li E, Bestor TH, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell. 1992;69(6):915–26.

    PubMed  CAS  Google Scholar 

  11. Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999;99(3):247–57.

    PubMed  CAS  Google Scholar 

  12. Dennis K, Fan T, Geiman T, Yan Q, Muegge K. Lsh, a member of the SNF2 family, is required for genome-wide methylation. Genes Dev. 2001;15(22):2940–4.

    PubMed  CAS  Google Scholar 

  13. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev. 2002;3(6):415–28.

    CAS  Google Scholar 

  14. Chen W, Cooper TK, Zahnow CA, et al. Epigenetic and genetic loss of Hic1 function accentuates the role of p53 in tumorigenesis. Cancer Cell. 2004;6(4):387–98.

    PubMed  CAS  Google Scholar 

  15. Yu L, Liu C, Vandeusen J, et al. Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia. Nat Genet. 2005;37(3):265–74.

    PubMed  CAS  Google Scholar 

  16. Leonhardt H, Page AW, Weier HU, Bestor TH. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell. 1992;71(5):865–73.

    PubMed  CAS  Google Scholar 

  17. Liu Y, Oakeley EJ, Sun L, Jost JP. Multiple domains are involved in the targeting of the mouse DNA methyltransferase to the DNA replication foci. Nucleic Acids Res. 1998;26(4):1038–45.

    PubMed  CAS  Google Scholar 

  18. Bostick M, Kim JK, Esteve PO, Clark A, Pradhan S, Jacobsen SE. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science. 2007;317(5845):1760–4.

    PubMed  CAS  Google Scholar 

  19. Mayer W, Niveleau A, Walter J, Fundele R, Haaf T. Demethylation of the zygotic paternal genome. Nature. 2000; 403(6769):501–2.

    PubMed  CAS  Google Scholar 

  20. Oswald J, Engemann S, Lane N, et al. Active demethylation of the paternal genome in the mouse zygote. Curr Biol. 2000;10(8):475–8.

    PubMed  CAS  Google Scholar 

  21. Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development. Science. 2001;293(5532):1089–93.

    PubMed  CAS  Google Scholar 

  22. Nakamura T, Arai Y, Umehara H, et al. PGC7/Stella protects against DNA demethylation in early embryogenesis. Nat Cell Biol. 2007;9(1):64–71.

    PubMed  CAS  Google Scholar 

  23. Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK. Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming. J Biol Chem. 2004;279(50):52353–60.

    PubMed  CAS  Google Scholar 

  24. Barreto G, Schafer A, Marhold J, et al. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature. 2007;445(7128):671–5.

    PubMed  CAS  Google Scholar 

  25. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292(5819):154–6.

    PubMed  CAS  Google Scholar 

  26. Bradley A, Evans M, Kaufman MH, Robertson E. Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature. 1984;309(5965):255–6.

    PubMed  CAS  Google Scholar 

  27. Kanatsu-Shinohara M, Toyokuni S, Shinohara T. Genetic selection of mouse male germline stem cells in vitro: offspring from single stem cells. Biol Reprod. 2005;72(1):236–40.

    PubMed  CAS  Google Scholar 

  28. Surani MA, Hayashi K, Hajkova P. Genetic and epigenetic regulators of pluripotency. Cell. 2007;128(4):747–62.

    PubMed  CAS  Google Scholar 

  29. Scholer HR. Octamania: the POU factors in murine development. Trends Genet. 1991;7(10):323–9.

    PubMed  CAS  Google Scholar 

  30. Herr W, Cleary MA. The POU domain: versatility in transcriptional regulation by a flexible two-in-one DNA-binding domain. Genes Dev. 1995;9(14):1679–93.

    PubMed  CAS  Google Scholar 

  31. Nichols J, Zevnik B, Anastassiadis K, et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell. 1998;95(3):379–91.

    PubMed  CAS  Google Scholar 

  32. Niwa H, Miyazaki J, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet. 2000;24(4):372–6.

    PubMed  CAS  Google Scholar 

  33. Chambers I, Colby D, Robertson M, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003;113(5):643–55.

    PubMed  CAS  Google Scholar 

  34. Mitsui K, Tokuzawa Y, Itoh H, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003;113(5):631–42.

    PubMed  CAS  Google Scholar 

  35. Darr H, Mayshar Y, Benvenisty N. Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development. 2006;133(6): 1193–201.

    PubMed  CAS  Google Scholar 

  36. Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 2003;17(1):126–40.

    PubMed  CAS  Google Scholar 

  37. Wood HB, Episkopou V. Comparative expression of the mouse Sox1, Sox2 and Sox3 genes from pre-gastrulation to early somite stages. Mech Dev. 1999;86(1–2):197–201.

    PubMed  CAS  Google Scholar 

  38. Ivanova N, Dobrin R, Lu R, et al. Dissecting self-renewal in stem cells with RNA interference. Nature. 2006;442(7102): 533–8.

    PubMed  CAS  Google Scholar 

  39. Boyer LA, Lee TI, Cole MF, et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005;122(6): 947–56.

    PubMed  CAS  Google Scholar 

  40. Boyer LA, Mathur D, Jaenisch R. Molecular control of pluripotency. Curr Opin Genet Dev. 2006;16(5):455–62.

    PubMed  CAS  Google Scholar 

  41. Loh YH, Wu Q, Chew JL, et al. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet. 2006;38(4):431–40.

    PubMed  CAS  Google Scholar 

  42. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.

    PubMed  CAS  Google Scholar 

  43. Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007; 448(7151):313–7.

    PubMed  CAS  Google Scholar 

  44. Wernig M, Meissner A, Foreman R, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature. 2007;448(7151):318–24.

    PubMed  CAS  Google Scholar 

  45. Rowland BD, Peeper DS. KLF4, p21 and context-dependent opposing forces in cancer. Nat Rev Cancer. 2006;6(1):11–23.

    PubMed  CAS  Google Scholar 

  46. Knoepfler PS. Myc goes global: new tricks for an old oncogene. Cancer Res. 2007;67(11):5061–3.

    PubMed  CAS  Google Scholar 

  47. Li Y, McClintick J, Zhong L, Edenberg HJ, Yoder MC, Chan RJ. Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4. Blood. 2005;105(2):635–7.

    PubMed  CAS  Google Scholar 

  48. Cartwright P, McLean C, Sheppard A, Rivett D, Jones K, Dalton S. LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism. Development. 2005;132(5): 885–96.

    PubMed  CAS  Google Scholar 

  49. Loh YH, Zhang W, Chen X, George J, Ng HH. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev. 2007;21(20):2545–57.

    PubMed  CAS  Google Scholar 

  50. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72.

    PubMed  CAS  Google Scholar 

  51. Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–20

    PubMed  CAS  Google Scholar 

  52. Richards M, Tan SP, Tan JH, Chan WK, Bongso A. The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells. 2004;22(1):51–64.

    PubMed  CAS  Google Scholar 

  53. Meshorer E, Yellajoshula D, George E, Scambler PJ, Brown DT, Misteli T. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Developmental Cell. 2006;10(1):105–16.

    PubMed  CAS  Google Scholar 

  54. Azuara V, Perry P, Sauer S, et al. Chromatin signatures of pluripotent cell lines. Nat Cell Biol. 2006;8(5):532–8.

    PubMed  CAS  Google Scholar 

  55. Bernstein BE, Mikkelsen TS, Xie X, et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 2006;125(2):315–26.

    PubMed  CAS  Google Scholar 

  56. Pan G, Tian S, Nie J, et al. Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells. Cell Stem Cell. 2007;1(3): :299–312.

    PubMed  CAS  Google Scholar 

  57. Zhao XD, Han X, Chew JL, et al. Whole-genome mapping of histone h3 lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells. Cell Stem Cell. 2007;1(3):286–98.

    PubMed  CAS  Google Scholar 

  58. Frank D, Keshet I, Shani M, Levine A, Razin A, Cedar H. Demethylation of CpG islands in embryonic cells. Nature. 1991;351(6323):239–41.

    PubMed  CAS  Google Scholar 

  59. Bibikova M, Chudin E, Wu B, et al. Human embryonic stem cells have a unique epigenetic signature. Genome Res. 2006;16(9):1075–83.

    PubMed  CAS  Google Scholar 

  60. Jahner D, Stuhlmann H, Stewart CL, et al. De novo methylation and expression of retroviral genomes during mouse embryogenesis. Nature. 1982;298(5875):623–8.

    PubMed  CAS  Google Scholar 

  61. Stewart CL, Stuhlmann H, Jahner D, Jaenisch R. De novo methylation, expression, and infectivity of retroviral genomes introduced into embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1982;79(13):4098–102.

    PubMed  CAS  Google Scholar 

  62. Brandeis M, Frank D, Keshet I, et al. Sp1 elements protect a CpG island from de novo methylation. Nature. 1994;371(6496):435–8.

    PubMed  CAS  Google Scholar 

  63. Jackson M, Krassowska A, Gilbert N, et al. Severe global DNA hypomethylation blocks differentiation and induces histone hyperacetylation in embryonic stem cells. Mol Cell Biol. 2004;24(20):8862–71.

    PubMed  CAS  Google Scholar 

  64. Tsumura A, Hayakawa T, Kumaki Y, et al. Maintenance of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. Genes Cells. 2006;11(7):805–14.

    PubMed  CAS  Google Scholar 

  65. Bourc’his D, Xu GL, Lin CS, Bollman B, Bestor TH. Dnmt3L and the establishment of maternal genomic imprints. Science. 2001;294(5551):2536–9.

    PubMed  Google Scholar 

  66. Bourc’his D, Bestor TH. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature. 2004;431(7004):96–9.

    PubMed  Google Scholar 

  67. Hata K, Okano M, Lei H, Li E. Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development. 2002;129(8):1983–93.

    PubMed  CAS  Google Scholar 

  68. Ooi SK, Qiu C, Bernstein E, et al. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature. 2007;448(7154):714–7.

    PubMed  CAS  Google Scholar 

  69. Jia D, Jurkowska RZ, Zhang X, Jeltsch A, Cheng X. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature. 2007;449(7159):248–51.

    PubMed  CAS  Google Scholar 

  70. Chen T, Ueda Y, Xie S, Li E. A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation. J Biol Chem. 2002;277(41):38746–54.

    PubMed  CAS  Google Scholar 

  71. Kaneda M, Okano M, Hata K, et al. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature. 2004;429(6994):900–3.

    PubMed  CAS  Google Scholar 

  72. Zhu H, Geiman TM, Xi S, et al. Lsh is involved in de novo methylation of DNA. EMBO J. 2006;25(2):335–45.

    PubMed  CAS  Google Scholar 

  73. Stein R, Razin A, Cedar H. In vitro methylation of the hamster adenine phosphoribosyltransferase gene inhibits its expression in mouse L cells. Proc Natl Acad Sci U S A. 1982;79(11):3418–22.

    PubMed  CAS  Google Scholar 

  74. Gidekel S, Bergman Y. A unique developmental pattern of Oct-3/4 DNA methylation is controlled by a cis-demodification element. J Biol Chem. 2002;277(37):34521–30.

    PubMed  CAS  Google Scholar 

  75. Feldman N, Gerson A, Fang J, et al. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat Cell Biol. 2006;8(2):188–94.

    PubMed  CAS  Google Scholar 

  76. Hattori N, Imao Y, Nishino K, et al. Epigenetic regulation of Nanog gene in embryonic stem and trophoblast stem cells. Genes Cells. 2007;12(3):387–96.

    PubMed  CAS  Google Scholar 

  77. Imamura M, Miura K, Iwabuchi K, et al. Transcriptional repression and DNA hypermethylation of a small set of ES cell marker genes in male germline stem cells. BMC Dev Biol 2006;6:34.

    PubMed  Google Scholar 

  78. Xu J, Pope SD, Jazirehi AR, et al. Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells. Proc Nat Acad Sci U S A. 2007;104(30):12377–82.

    CAS  Google Scholar 

  79. Lindroth AM, Cao X, Jackson JP, et al. Requirement of CHROMOMETHYLASE3 for maintenance of CpXpG methylation. Science. 2001;292(5524):2077–80.

    PubMed  CAS  Google Scholar 

  80. Gruenbaum Y, Stein R, Cedar H, Razin A. Methylation of CpG sequences in eukaryotic DNA. FEBS Lett. 1981;124(1):67–71.

    PubMed  CAS  Google Scholar 

  81. Ramsahoye BH, Biniszkiewicz D, Lyko F, Clark V, Bird AP, Jaenisch R. Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc Natl Acad Sci U S A. 2000;97(10):5237–42.

    PubMed  CAS  Google Scholar 

  82. Eden A, Gaudet F, Waghmare A, Jaenisch R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science. 2003;300(5618):455.

    PubMed  CAS  Google Scholar 

  83. Gaudet F, Hodgson JG, Eden A, et al. Induction of tumors in mice by genomic hypomethylation. Science. 2003;300(5618):489–92.

    PubMed  CAS  Google Scholar 

  84. Lei H, Oh SP, Okano M, et al. De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development. 1996;122(10):3195–205.

    PubMed  CAS  Google Scholar 

  85. Carlone DL, Lee JH, Young SR, et al. Reduced genomic cytosine methylation and defective cellular differentiation in embryonic stem cells lacking CpG binding protein. Mol Cell Biol. 2005;25(12):4881–91.

    PubMed  CAS  Google Scholar 

  86. Tadokoro Y, Ema H, Okano M, Li E, Nakauchi H. De novo DNA methyltransferase is essential for self-renewal, but not for differentiation, in hematopoietic stem cells. J Exp Med. 2007;204(4):715–22.

    PubMed  CAS  Google Scholar 

  87. Gurdon JB. From nuclear transfer to nuclear reprogramming: the reversal of cell differentiation. Annu Rev Cell Dev Biol. 2006;22:1–22.

    PubMed  CAS  Google Scholar 

  88. Tada M, Takahama Y, Abe K, Nakatsuji N, Tada T. Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol. 2001;11(19):1553–8.

    PubMed  CAS  Google Scholar 

  89. Bannister AJ, Zegerman P, Partridge JF, et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature. 2001;410(6824):120–4.

    PubMed  CAS  Google Scholar 

  90. Rea S, Eisenhaber F, O’Carroll D, et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature. 2000;406(6796):593–9.

    PubMed  CAS  Google Scholar 

  91. Tachibana M, Sugimoto K, Nozaki M, et al. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev. 2002;16(14):1779–91.

    PubMed  CAS  Google Scholar 

  92. Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y. A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. Science. 2002;296(5570): 1132–6.

    PubMed  CAS  Google Scholar 

  93. Yang L, Xia L, Wu DY, et al. Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor. Oncogene. 2002;21(1):148–52.

    PubMed  CAS  Google Scholar 

  94. Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ, 3rd. SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev. 2002;16(8):919–32.

    PubMed  CAS  Google Scholar 

  95. Peters AH, Kubicek S, Mechtler K, et al. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell. 2003;12(6):1577–89.

    PubMed  CAS  Google Scholar 

  96. Rice JC, Briggs SD, Ueberheide B, et al. Histone methyltransferases direct different degrees of methylation to define distinct chromatin domains. Mol Cell. 2003;12(6):1591–8.

    PubMed  CAS  Google Scholar 

  97. Vire E, Brenner C, Deplus R, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006;439(7078):871–4.

    PubMed  CAS  Google Scholar 

  98. Freitag M, Hickey PC, Khlafallah TK, Read ND, Selker EU. HP1 is essential for DNA methylation in neurospora. Mol Cell. 2004;13(3):427–34.

    PubMed  CAS  Google Scholar 

  99. Lehnertz B, Ueda Y, Derijck AA, et al. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol. 2003;13(14):1192–200.

    PubMed  CAS  Google Scholar 

  100. Jackson JP, Lindroth AM, Cao X, Jacobsen SE. Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature. 2002;416(6880):556–60.

    PubMed  CAS  Google Scholar 

  101. Vassen L, Fiolka K, Moroy T. Gfi1b alters histone methylation at target gene promoters and sites of gamma-satellite containing heterochromatin. EMBO J. 2006;25(11):2409–19.

    PubMed  CAS  Google Scholar 

  102. Fuks F, Hurd PJ, Deplus R, Kouzarides T. The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res. 2003;31(9):2305–12.

    PubMed  CAS  Google Scholar 

  103. Smallwood A, Esteve PO, Pradhan S, Carey M. Functional cooperation between HP1 and DNMT1 mediates gene silencing. Genes Dev. 2007;21(10):1169–78.

    PubMed  CAS  Google Scholar 

  104. Tachibana M, Ueda J, Fukuda M, et al. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev. 2005;19(7):815–26.

    PubMed  CAS  Google Scholar 

  105. Ikegami K, Iwatani M, Suzuki M, et al. Genome-wide and locus-specific DNA hypomethylation in G9a deficient mouse embryonic stem cells. Genes Cells. 2007;12(1):1–11.

    PubMed  CAS  Google Scholar 

  106. Xin Z, Tachibana M, Guggiari M, Heard E, Shinkai Y, Wagstaff J. Role of histone methyltransferase G9a in CpG methylation of the Prader-Willi syndrome imprinting center. J Biol Chem. 2003;278(17):14996–5000.

    PubMed  CAS  Google Scholar 

  107. Epsztejn-Litman S, Feldman N, Abu-Remaileh M, et al. De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes. Nat Struct Mol Biol. In press.

    Google Scholar 

  108. McGarvey KM, Fahrner JA, Greene E, Martens J, Jenuwein T, Baylin SB. Silenced tumor suppressor genes reactivated by DNA demethylation do not return to a fully euchromatic chromatin state. Cancer Res. 2006;66(7):3541–9.

    PubMed  CAS  Google Scholar 

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  1. The Hubert Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University Medical School, Ein Kerem, Jerusalem, 91120, Israel

    Monther Abu-Remaileh & Yehudit Bergman

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  1. Monther Abu-Remaileh
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Correspondence to Yehudit Bergman .

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  1. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Vinagolu K. Rajasekhar MSc, MPhil, PhD

  2. Invitrogen Corporation, Frederick, MD, USA

    Mohan C. Vemuri Ph.D.

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Abu-Remaileh, M., Bergman, Y. (2009). Epigenetic Signature of Embryonal Stem Cells: A DNA Methylation Perspective. In: Rajasekhar, V.K., Vemuri, M.C. (eds) Regulatory Networks in Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-60327-227-8_20

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