1932

Abstract

DNA methylation at the 5-position of cytosine (5mC) plays vital roles in mammalian development. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), and the two DNMT families, DNMT3 and DNMT1, are responsible for methylation establishment and maintenance, respectively. Since their discovery, biochemical and structural studies have revealed the key mechanisms underlying how DNMTs catalyze de novo and maintenance DNA methylation. In particular, recent development of low-input genomic and epigenomic technologies has deepened our understanding of DNA methylation regulation in germ lines and early stage embryos. In this review, we first describe the methylation machinery including the DNMTs and their essential cofactors. We then discuss how DNMTs are recruited to or excluded from certain genomic elements. Lastly, we summarize recent understanding of the regulation of DNA methylation dynamics in mammalian germ lines and early embryos with a focus on both mice and humans.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biochem-103019-102815
2020-06-20
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/biochem/89/1/annurev-biochem-103019-102815.html?itemId=/content/journals/10.1146/annurev-biochem-103019-102815&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Goll MG, Bestor TH. 2005. Eukaryotic cytosine methyltransferases. Annu. Rev. Biochem. 74:481–514
    [Google Scholar]
  2. 2. 
    Smith ZD, Meissner A. 2013. DNA methylation: roles in mammalian development. Nat. Rev. Genet. 14:204–20
    [Google Scholar]
  3. 3. 
    Li E, Zhang Y. 2014. DNA methylation in mammals. Cold Spring Harb. Perspect. Biol. 6:a019133
    [Google Scholar]
  4. 4. 
    Jain D, Meydan C, Lange J, Claeys Bouuaert C, Lailler N et al. 2017. rahu is a mutant allele of Dnmt3c, encoding a DNA methyltransferase homolog required for meiosis and transposon repression in the mouse male germline. PLOS Genet 13:e1006964
    [Google Scholar]
  5. 5. 
    Barau J, Teissandier A, Zamudio N, Roy S, Nalesso V et al. 2016. The DNA methyltransferase DNMT3C protects male germ cells from transposon activity. Science 354:909–12
    [Google Scholar]
  6. 6. 
    Okano M, Bell DW, Haber DA, Li E 1999. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–57
    [Google Scholar]
  7. 7. 
    Bourc'his D, Bestor TH. 2004. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431:96–99
    [Google Scholar]
  8. 8. 
    Bourc'his D, Xu GL, Lin CS, Bollman B, Bestor TH 2001. Dnmt3L and the establishment of maternal genomic imprints. Science 294:2536–39
    [Google Scholar]
  9. 9. 
    Kaneda M, Okano M, Hata K, Sado T, Tsujimoto N et al. 2004. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429:900–3
    [Google Scholar]
  10. 10. 
    Li E, Bestor TH, Jaenisch R 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–26
    [Google Scholar]
  11. 11. 
    Deaton AM, Bird A. 2011. CpG islands and the regulation of transcription. Genes Dev 25:1010–22
    [Google Scholar]
  12. 12. 
    Wu X, Zhang Y. 2017. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat. Rev. Genet. 18:517–34
    [Google Scholar]
  13. 13. 
    Messerschmidt DM, Knowles BB, Solter D 2014. DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev 28:812–28
    [Google Scholar]
  14. 14. 
    Zhang H, Lang Z, Zhu JK 2018. Dynamics and function of DNA methylation in plants. Nat. Rev. Mol. Cell Biol. 19:489–506
    [Google Scholar]
  15. 15. 
    Huff JT, Zilberman D. 2014. Dnmt1-independent CG methylation contributes to nucleosome positioning in diverse eukaryotes. Cell 156:1286–97
    [Google Scholar]
  16. 16. 
    Lyko F. 2018. The DNA methyltransferase family: a versatile toolkit for epigenetic regulation. Nat. Rev. Genet. 19:81–92
    [Google Scholar]
  17. 17. 
    Ooi SK, Qiu C, Bernstein E, Li K, Jia D et al. 2007. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448:714–17
    [Google Scholar]
  18. 18. 
    Guo X, Wang L, Li J, Ding Z, Xiao J et al. 2015. Structural insight into autoinhibition and histone H3-induced activation of DNMT3A. Nature 517:640–44
    [Google Scholar]
  19. 19. 
    Wagner EJ, Carpenter PB. 2012. Understanding the language of Lys36 methylation at histone H3. Nat. Rev. Mol. Cell Biol. 13:115–26
    [Google Scholar]
  20. 20. 
    Ge YZ, Pu MT, Gowher H, Wu HP, Ding JP et al. 2004. Chromatin targeting of de novo DNA methyltransferases by the PWWP domain. J. Biol. Chem. 279:25447–54
    [Google Scholar]
  21. 21. 
    Baubec T, Colombo DF, Wirbelauer C, Schmidt J, Burger L et al. 2015. Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. Nature 520:243–47
    [Google Scholar]
  22. 22. 
    Heyn P, Logan CV, Fluteau A, Challis RC, Auchynnikava T et al. 2019. Gain-of-function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions. Nat. Genet. 51:96–105
    [Google Scholar]
  23. 23. 
    Sendzikaite G, Hanna CW, Stewart-Morgan KR, Ivanova E, Kelsey G 2019. A DNMT3A PWWP mutation leads to methylation of bivalent chromatin and growth retardation in mice. Nat. Commun. 10:1884
    [Google Scholar]
  24. 24. 
    Chedin F, Lieber MR, Hsieh CL 2002. The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a. PNAS 99:16916–21
    [Google Scholar]
  25. 25. 
    Jia D, Jurkowska RZ, Zhang X, Jeltsch A, Cheng X 2007. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature 449:248–51
    [Google Scholar]
  26. 26. 
    Zhang ZM, Lu R, Wang P, Yu Y, Chen D et al. 2018. Structural basis for DNMT3A-mediated de novo DNA methylation. Nature 554:387–91
    [Google Scholar]
  27. 27. 
    Veland N, Lu Y, Hardikar S, Gaddis S, Zeng Y et al. 2019. DNMT3L facilitates DNA methylation partly by maintaining DNMT3A stability in mouse embryonic stem cells. Nucleic Acids Res 47:152–67
    [Google Scholar]
  28. 28. 
    Manzo M, Wirz J, Ambrosi C, Villasenor R, Roschitzki B, Baubec T 2017. Isoform-specific localization of DNMT3A regulates DNA methylation fidelity at bivalent CpG islands. EMBO J 36:3421–34
    [Google Scholar]
  29. 29. 
    Gu T, Lin X, Cullen SM, Luo M, Jeong M et al. 2018. DNMT3A and TET1 cooperate to regulate promoter epigenetic landscapes in mouse embryonic stem cells. Genome Biol 19:88
    [Google Scholar]
  30. 30. 
    Duymich CE, Charlet J, Yang X, Jones PA, Liang G 2016. DNMT3B isoforms without catalytic activity stimulate gene body methylation as accessory proteins in somatic cells. Nat. Commun. 7:11453
    [Google Scholar]
  31. 31. 
    Liao J, Karnik R, Gu H, Ziller MJ, Clement K et al. 2015. Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells. Nat. Genet. 47:469–78
    [Google Scholar]
  32. 32. 
    Rountree MR, Bachman KE, Baylin SB 2000. DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nat. Genet. 25:269–77
    [Google Scholar]
  33. 33. 
    Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF 1997. Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science 277:1996–2000
    [Google Scholar]
  34. 34. 
    Nishiyama A, Yamaguchi L, Sharif J, Johmura Y, Kawamura T et al. 2013. Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication. Nature 502:249–53
    [Google Scholar]
  35. 35. 
    Ishiyama S, Nishiyama A, Saeki Y, Moritsugu K, Morimoto D et al. 2017. Structure of the Dnmt1 reader module complexed with a unique two-mono-ubiquitin mark on histone H3 reveals the basis for DNA methylation maintenance. Mol. Cell 68:350–60.e7
    [Google Scholar]
  36. 36. 
    Qin W, Wolf P, Liu N, Link S, Smets M et al. 2015. DNA methylation requires a DNMT1 ubiquitin interacting motif (UIM) and histone ubiquitination. Cell Res 25:911–29
    [Google Scholar]
  37. 37. 
    Takeshita K, Suetake I, Yamashita E, Suga M, Narita H et al. 2011. Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1). PNAS 108:9055–59
    [Google Scholar]
  38. 38. 
    Song J, Rechkoblit O, Bestor TH, Patel DJ 2011. Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation. Science 331:1036–40
    [Google Scholar]
  39. 39. 
    Yarychkivska O, Shahabuddin Z, Comfort N, Boulard M, Bestor TH 2018. BAH domains and a histone-like motif in DNA methyltransferase 1 (DNMT1) regulate de novo and maintenance methylation in vivo. J. Biol. Chem. 293:19466–75
    [Google Scholar]
  40. 40. 
    Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A et al. 2007. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature 450:908–12
    [Google Scholar]
  41. 41. 
    Bostick M, Kim JK, Esteve PO, Clark A, Pradhan S, Jacobsen SE 2007. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 317:1760–64
    [Google Scholar]
  42. 42. 
    Xie S, Qian C. 2018. The growing complexity of UHRF1-mediated maintenance DNA methylation. Genes 9:600
    [Google Scholar]
  43. 43. 
    Hashimoto H, Horton JR, Zhang X, Bostick M, Jacobsen SE, Cheng X 2008. The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix. Nature 455:826–29
    [Google Scholar]
  44. 44. 
    Avvakumov GV, Walker JR, Xue S, Li Y, Duan S et al. 2008. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature 455:822–25
    [Google Scholar]
  45. 45. 
    Arita K, Ariyoshi M, Tochio H, Nakamura Y, Shirakawa M 2008. Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism. Nature 455:818–21
    [Google Scholar]
  46. 46. 
    Rajakumara E, Wang Z, Ma H, Hu L, Chen H et al. 2011. PHD finger recognition of unmodified histone H3R2 links UHRF1 to regulation of euchromatic gene expression. Mol. Cell 43:275–84
    [Google Scholar]
  47. 47. 
    Rothbart SB, Krajewski K, Nady N, Tempel W, Xue S et al. 2012. Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation. Nat. Struct. Mol. Biol. 19:1155–60
    [Google Scholar]
  48. 48. 
    Li T, Wang L, Du Y, Xie S, Yang X et al. 2018. Structural and mechanistic insights into UHRF1-mediated DNMT1 activation in the maintenance DNA methylation. Nucleic Acids Res 46:3218–31
    [Google Scholar]
  49. 49. 
    Yarychkivska O, Tavana O, Gu W, Bestor TH 2018. Independent functions of DNMT1 and USP7 at replication foci. Epigenet. Chromatin 11:9
    [Google Scholar]
  50. 50. 
    Howell CY, Bestor TH, Ding F, Latham KE, Mertineit C et al. 2001. Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 104:829–38
    [Google Scholar]
  51. 51. 
    Hirasawa R, Chiba H, Kaneda M, Tajima S, Li E et al. 2008. Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development. Genes Dev 22:1607–16
    [Google Scholar]
  52. 52. 
    Xie W, Schultz MD, Lister R, Hou Z, Rajagopal N et al. 2013. Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell 153:1134–48
    [Google Scholar]
  53. 53. 
    Macleod D, Charlton J, Mullins J, Bird AP 1994. Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev 8:2282–92
    [Google Scholar]
  54. 54. 
    Brandeis M, Frank D, Keshet I, Siegfried Z, Mendelsohn M et al. 1994. Sp1 elements protect a CpG island from de novo methylation. Nature 371:435–38
    [Google Scholar]
  55. 55. 
    Li Y, Zheng H, Wang Q, Zhou C, Wei L et al. 2018. Genome-wide analyses reveal a role of Polycomb in promoting hypomethylation of DNA methylation valleys. Genome Biol 19:18
    [Google Scholar]
  56. 56. 
    Boulard M, Edwards JR, Bestor TH 2015. FBXL10 protects Polycomb-bound genes from hypermethylation. Nat. Genet. 47:479–85
    [Google Scholar]
  57. 57. 
    Zhang Y, Charlton J, Karnik R, Beerman I, Smith ZD et al. 2018. Targets and genomic constraints of ectopic Dnmt3b expression. eLife 7:e40757
    [Google Scholar]
  58. 58. 
    Mohn F, Weber M, Rebhan M, Roloff TC, Richter J et al. 2008. Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. Mol. Cell 30:755–66
    [Google Scholar]
  59. 59. 
    Carlone DL, Lee JH, Young SR, Dobrota E, Butler JS et al. 2005. Reduced genomic cytosine methylation and defective cellular differentiation in embryonic stem cells lacking CpG binding protein. Mol. Cell. Biol. 25:4881–91
    [Google Scholar]
  60. 60. 
    Wu H, Zhang Y. 2014. Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell 156:45–68
    [Google Scholar]
  61. 61. 
    Wu H, D'Alessio AC, Ito S, Xia K, Wang Z et al. 2011. Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature 473:389–93
    [Google Scholar]
  62. 62. 
    Lu F, Liu Y, Jiang L, Yamaguchi S, Zhang Y 2014. Role of Tet proteins in enhancer activity and telomere elongation. Genes Dev 28:2103–19
    [Google Scholar]
  63. 63. 
    Dai HQ, Wang BA, Yang L, Chen JJ, Zhu GC et al. 2016. TET-mediated DNA demethylation controls gastrulation by regulating Lefty–Nodal signalling. Nature 538:528–32
    [Google Scholar]
  64. 64. 
    Verma N, Pan H, Dore LC, Shukla A, Li QV et al. 2018. TET proteins safeguard bivalent promoters from de novo methylation in human embryonic stem cells. Nat. Genet. 50:83–95
    [Google Scholar]
  65. 65. 
    Ginno PA, Lott PL, Christensen HC, Korf I, Chedin F 2012. R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters. Mol. Cell 45:814–25
    [Google Scholar]
  66. 66. 
    Arab K, Karaulanov E, Musheev M, Trnka P, Schafer A et al. 2019. GADD45A binds R-loops and recruits TET1 to CpG island promoters. Nat. Genet. 51:217–23
    [Google Scholar]
  67. 67. 
    Schüle KM, Leichsenring M, Andreani T, Vastolo V, Mallick M et al. 2019. GADD45 promotes locus-specific DNA demethylation and 2C cycling in embryonic stem cells. Genes Dev 33:782–98
    [Google Scholar]
  68. 68. 
    Borgel J, Guibert S, Li Y, Chiba H, Schubeler D et al. 2010. Targets and dynamics of promoter DNA methylation during early mouse development. Nat. Genet. 42:1093–100
    [Google Scholar]
  69. 69. 
    Auclair G, Guibert S, Bender A, Weber M 2014. Ontogeny of CpG island methylation and specificity of DNMT3 methyltransferases during embryonic development in the mouse. Genome Biol 15:545
    [Google Scholar]
  70. 70. 
    Auclair G, Borgel J, Sanz LA, Vallet J, Guibert S et al. 2016. EHMT2 directs DNA methylation for efficient gene silencing in mouse embryos. Genome Res 26:192–202
    [Google Scholar]
  71. 71. 
    Velasco G, Hube F, Rollin J, Neuillet D, Philippe C et al. 2010. Dnmt3b recruitment through E2F6 transcriptional repressor mediates germ-line gene silencing in murine somatic tissues. PNAS 107:9281–86
    [Google Scholar]
  72. 72. 
    Feldman N, Gerson A, Fang J, Li E, Zhang Y et al. 2006. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat. Cell Biol. 8:188–94
    [Google Scholar]
  73. 73. 
    Tachibana M, Matsumura Y, Fukuda M, Kimura H, Shinkai Y 2008. G9a/GLP complexes independently mediate H3K9 and DNA methylation to silence transcription. EMBO J 27:2681–90
    [Google Scholar]
  74. 74. 
    Dong KB, Maksakova IA, Mohn F, Leung D, Appanah R et al. 2008. DNA methylation in ES cells requires the lysine methyltransferase G9a but not its catalytic activity. EMBO J 27:2691–701
    [Google Scholar]
  75. 75. 
    Zhang Y, Xiang Y, Yin Q, Du Z, Peng X et al. 2018. Dynamic epigenomic landscapes during early lineage specification in mouse embryos. Nat. Genet. 50:96–105
    [Google Scholar]
  76. 76. 
    Maunakea AK, Nagarajan RP, Bilenky M, Ballinger TJ, D'Souza C et al. 2010. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature 466:253–57
    [Google Scholar]
  77. 77. 
    Neri F, Rapelli S, Krepelova A, Incarnato D, Parlato C et al. 2017. Intragenic DNA methylation prevents spurious transcription initiation. Nature 543:72–77
    [Google Scholar]
  78. 78. 
    Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK et al. 1999. The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. PNAS 96:14412–17
    [Google Scholar]
  79. 79. 
    Gatto S, Gagliardi M, Franzese M, Leppert S, Papa M et al. 2017. ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing. Nucleic Acids Res 45:5739–56
    [Google Scholar]
  80. 80. 
    Singh S, Narayanan SP, Biswas K, Gupta A, Ahuja N et al. 2017. Intragenic DNA methylation and BORIS-mediated cancer-specific splicing contribute to the Warburg effect. PNAS 114:11440–45
    [Google Scholar]
  81. 81. 
    Walsh CP, Chaillet JR, Bestor TH 1998. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat. Genet. 20:116–17
    [Google Scholar]
  82. 82. 
    Deniz O, Frost JM, Branco MR 2019. Regulation of transposable elements by DNA modifications. Nat. Rev. Genet. 20:417–31
    [Google Scholar]
  83. 83. 
    Wolf G, Yang P, Fuchtbauer AC, Fuchtbauer EM, Silva AM et al. 2015. The KRAB zinc finger protein ZFP809 is required to initiate epigenetic silencing of endogenous retroviruses. Genes Dev 29:538–54
    [Google Scholar]
  84. 84. 
    Leung DC, Dong KB, Maksakova IA, Goyal P, Appanah R et al. 2011. Lysine methyltransferase G9a is required for de novo DNA methylation and the establishment, but not the maintenance, of proviral silencing. PNAS 108:5718–23
    [Google Scholar]
  85. 85. 
    Bulut-Karslioglu A, De La Rosa-Velazquez IA, Ramirez F, Barenboim M, Onishi-Seebacher M et al. 2014. Suv39h-dependent H3K9me3 marks intact retrotransposons and silences LINE elements in mouse embryonic stem cells. Mol. Cell 55:277–90
    [Google Scholar]
  86. 86. 
    Karimi MM, Goyal P, Maksakova IA, Bilenky M, Leung D et al. 2011. DNA methylation and SETDB1/H3K9me3 regulate predominantly distinct sets of genes, retroelements, and chimeric transcripts in mESCs. Cell Stem Cell 8:676–87
    [Google Scholar]
  87. 87. 
    Walter M, Teissandier A, Pérez-Palacios R, Bourc'his D 2016. An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells. eLife 5:e11418
    [Google Scholar]
  88. 88. 
    Seisenberger S, Andrews S, Krueger F, Arand J, Walter J et al. 2012. The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol. Cell 48:849–62
    [Google Scholar]
  89. 89. 
    Guibert S, Forne T, Weber M 2012. Global profiling of DNA methylation erasure in mouse primordial germ cells. Genome Res 22:633–41
    [Google Scholar]
  90. 90. 
    Hackett JA, Sengupta R, Zylicz JJ, Murakami K, Lee C et al. 2013. Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine. Science 339:448–52
    [Google Scholar]
  91. 91. 
    Yamaguchi S, Hong K, Liu R, Inoue A, Shen L et al. 2013. Dynamics of 5-methylcytosine and 5-hydroxymethylcytosine during germ cell reprogramming. Cell Res 23:329–39
    [Google Scholar]
  92. 92. 
    Yamaguchi S, Hong K, Liu R, Shen L, Inoue A et al. 2012. Tet1 controls meiosis by regulating meiotic gene expression. Nature 492:443–47
    [Google Scholar]
  93. 93. 
    Yamaguchi S, Shen L, Liu Y, Sendler D, Zhang Y 2013. Role of Tet1 in erasure of genomic imprinting. Nature 504:460–64
    [Google Scholar]
  94. 94. 
    Vincent JJ, Huang Y, Chen PY, Feng S, Calvopina JH et al. 2013. Stage-specific roles for Tet1 and Tet2 in DNA demethylation in primordial germ cells. Cell Stem Cell 12:470–78
    [Google Scholar]
  95. 95. 
    Hargan-Calvopina J, Taylor S, Cook H, Hu Z, Lee SA et al. 2016. Stage-specific demethylation in primordial germ cells safeguards against precocious differentiation. Dev. Cell 39:75–86
    [Google Scholar]
  96. 96. 
    Kagiwada S, Kurimoto K, Hirota T, Yamaji M, Saitou M 2013. Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice. EMBO J 32:340–53
    [Google Scholar]
  97. 97. 
    Ohno R, Nakayama M, Naruse C, Okashita N, Takano O et al. 2013. A replication-dependent passive mechanism modulates DNA demethylation in mouse primordial germ cells. Development 140:2892–903
    [Google Scholar]
  98. 98. 
    Hill PWS, Leitch HG, Requena CE, Sun Z, Amouroux R et al. 2018. Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte. Nature 555:392–96
    [Google Scholar]
  99. 99. 
    Guo F, Yan L, Guo H, Li L, Hu B et al. 2015. The transcriptome and DNA methylome landscapes of human primordial germ cells. Cell 161:1437–52
    [Google Scholar]
  100. 100. 
    Guo H, Hu B, Yan L, Yong J, Wu Y et al. 2017. DNA methylation and chromatin accessibility profiling of mouse and human fetal germ cells. Cell Res 27:165–83
    [Google Scholar]
  101. 101. 
    Gkountela S, Zhang KX, Shafiq TA, Liao WW, Hargan-Calvopina J et al. 2015. DNA demethylation dynamics in the human prenatal germline. Cell 161:1425–36
    [Google Scholar]
  102. 102. 
    Shirane K, Toh H, Kobayashi H, Miura F, Chiba H et al. 2013. Mouse oocyte methylomes at base resolution reveal genome-wide accumulation of non-CpG methylation and role of DNA methyltransferases. PLOS Genet 9:e1003439
    [Google Scholar]
  103. 103. 
    Kobayashi H, Sakurai T, Imai M, Takahashi N, Fukuda A et al. 2012. Contribution of intragenic DNA methylation in mouse gametic DNA methylomes to establish oocyte-specific heritable marks. PLOS Genet 8:e1002440
    [Google Scholar]
  104. 104. 
    Smallwood SA, Tomizawa S, Krueger F, Ruf N, Carli N et al. 2011. Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat. Genet. 43:811–14
    [Google Scholar]
  105. 105. 
    Chotalia M, Smallwood SA, Ruf N, Dawson C, Lucifero D et al. 2009. Transcription is required for establishment of germline methylation marks at imprinted genes. Genes Dev 23:105–17
    [Google Scholar]
  106. 106. 
    Veselovska L, Smallwood SA, Saadeh H, Stewart KR, Krueger F et al. 2015. Deep sequencing and de novo assembly of the mouse oocyte transcriptome define the contribution of transcription to the DNA methylation landscape. Genome Biol 16:209
    [Google Scholar]
  107. 107. 
    Brind'Amour J, Kobayashi H, Richard Albert J, Shirane K, Sakashita A et al. 2018. LTR retrotransposons transcribed in oocytes drive species-specific and heritable changes in DNA methylation. Nat. Commun. 9:3331
    [Google Scholar]
  108. 108. 
    Kelsey G, Feil R. 2013. New insights into establishment and maintenance of DNA methylation imprints in mammals. Philos. Trans. R. Soc. B 368:20110336
    [Google Scholar]
  109. 109. 
    Dahl JA, Jung I, Aanes H, Greggains GD, Manaf A et al. 2016. Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition. Nature 537:548–52
    [Google Scholar]
  110. 110. 
    Zhang B, Zheng H, Huang B, Li W, Xiang Y et al. 2016. Allelic reprogramming of the histone modification H3K4me3 in early mammalian development. Nature 537:553–57
    [Google Scholar]
  111. 111. 
    Stewart KR, Veselovska L, Kim J, Huang J, Saadeh H et al. 2015. Dynamic changes in histone modifications precede de novo DNA methylation in oocytes. Genes Dev 29:2449–62
    [Google Scholar]
  112. 112. 
    Xu Q, Xiang Y, Wang Q, Wang L, Brind'Amour J et al. 2019. SETD2 regulates the maternal epigenome, genomic imprinting and embryonic development. Nat. Genet. 51:844–56
    [Google Scholar]
  113. 113. 
    Okae H, Chiba H, Hiura H, Hamada H, Sato A et al. 2014. Genome-wide analysis of DNA methylation dynamics during early human development. PLOS Genet 10:e1004868
    [Google Scholar]
  114. 114. 
    Guo H, Zhu P, Yan L, Li R, Hu B et al. 2014. The DNA methylation landscape of human early embryos. Nature 511:606–10
    [Google Scholar]
  115. 115. 
    Singh P, Li AX, Tran DA, Oates N, Kang ER et al. 2013. De novo DNA methylation in the male germ line occurs by default but is excluded at sites of H3K4 methylation. Cell Rep 4:205–19
    [Google Scholar]
  116. 116. 
    Zamudio N, Barau J, Teissandier A, Walter M, Borsos M et al. 2015. DNA methylation restrains transposons from adopting a chromatin signature permissive for meiotic recombination. Genes Dev 29:1256–70
    [Google Scholar]
  117. 117. 
    Czech B, Munafo M, Ciabrelli F, Eastwood EL, Fabry MH et al. 2018. piRNA-guided genome defense: from biogenesis to silencing. Annu. Rev. Genet. 52:131–57
    [Google Scholar]
  118. 118. 
    Pezic D, Manakov SA, Sachidanandam R, Aravin AA 2014. piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells. Genes Dev 28:1410–28
    [Google Scholar]
  119. 119. 
    Watanabe T, Tomizawa S, Mitsuya K, Totoki Y, Yamamoto Y et al. 2011. Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science 332:848–52
    [Google Scholar]
  120. 120. 
    Watanabe T, Cui X, Yuan Z, Qi H, Lin H 2018. MIWI2 targets RNAs transcribed from piRNA-dependent regions to drive DNA methylation in mouse prospermatogonia. EMBO J 37:e95329
    [Google Scholar]
  121. 121. 
    Marques CJ, Joao Pinho M, Carvalho F, Bieche I, Barros A, Sousa M 2011. DNA methylation imprinting marks and DNA methyltransferase expression in human spermatogenic cell stages. Epigenetics 6:1354–61
    [Google Scholar]
  122. 122. 
    Pitamber PN, Lombard Z, Ramsay M 2012. No evidence for a parent-of-origin specific differentially methylated region linked to RASGRF1. Front. Genet. 3:41
    [Google Scholar]
  123. 123. 
    Shen L, Inoue A, He J, Liu Y, Lu F, Zhang Y 2014. Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes. Cell Stem Cell 15:459–71
    [Google Scholar]
  124. 124. 
    Guo F, Li X, Liang D, Li T, Zhu P et al. 2014. Active and passive demethylation of male and female pronuclear DNA in the mammalian zygote. Cell Stem Cell 15:447–59
    [Google Scholar]
  125. 125. 
    Wang L, Zhang J, Duan J, Gao X, Zhu W et al. 2014. Programming and inheritance of parental DNA methylomes in mammals. Cell 157:979–91
    [Google Scholar]
  126. 126. 
    Amouroux R, Nashun B, Shirane K, Nakagawa S, Hill PW et al. 2016. De novo DNA methylation drives 5hmC accumulation in mouse zygotes. Nat. Cell Biol. 18:225–33
    [Google Scholar]
  127. 127. 
    Nakamura T, Arai Y, Umehara H, Masuhara M, Kimura T et al. 2007. PGC7/Stella protects against DNA demethylation in early embryogenesis. Nat. Cell Biol. 9:64–71
    [Google Scholar]
  128. 128. 
    Nakamura T, Liu YJ, Nakashima H, Umehara H, Inoue K et al. 2012. PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos. Nature 486:415–19
    [Google Scholar]
  129. 129. 
    Li Y, Zhang Z, Chen J, Liu W, Lai W et al. 2018. Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1. Nature 564:136–40
    [Google Scholar]
  130. 130. 
    Han L, Ren C, Zhang J, Shu W, Wang Q 2019. Differential roles of Stella in the modulation of DNA methylation during oocyte and zygotic development. Cell Discov 5:9
    [Google Scholar]
  131. 131. 
    Maenohara S, Unoki M, Toh H, Ohishi H, Sharif J et al. 2017. Role of UHRF1 in de novo DNA meth-ylation in oocytes and maintenance methylation in preimplantation embryos. PLOS Genet 13:e1007042
    [Google Scholar]
  132. 132. 
    Du W, Dong Q, Zhang Z, Liu B, Zhou T et al. 2019. Stella protein facilitates DNA demethylation by disrupting the chromatin association of the RING finger-type E3 ubiquitin ligase UHRF1. J. Biol. Chem. 294:8907–17
    [Google Scholar]
  133. 133. 
    Zeng TB, Han L, Pierce N, Pfeifer GP, Szabó PE 2019. EHMT2 and SETDB1 protect the maternal pronucleus from 5mC oxidation. PNAS 116:10834–41
    [Google Scholar]
  134. 134. 
    Au Yeung WK, Brind'Amour J, Hatano Y, Yamagata K, Feil R et al. 2019. Histone H3K9 methyltransferase G9a in oocytes is essential for preimplantation development but dispensable for CG methylation protection. Cell Rep 27:282–93.e4
    [Google Scholar]
  135. 135. 
    Smith ZD, Chan MM, Humm KC, Karnik R, Mekhoubad S et al. 2014. DNA methylation dynamics of the human preimplantation embryo. Nature 511:611–15
    [Google Scholar]
  136. 136. 
    Zhu P, Guo H, Ren Y, Hou Y, Dong J et al. 2018. Single-cell DNA methylome sequencing of human preimplantation embryos. Nat. Genet. 50:12–19
    [Google Scholar]
  137. 137. 
    Smith ZD, Chan MM, Mikkelsen TS, Gu H, Gnirke A et al. 2012. A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature 484:339–44
    [Google Scholar]
  138. 138. 
    Li X, Ito M, Zhou F, Youngson N, Zuo X et al. 2008. A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints. Dev. Cell 15:547–57
    [Google Scholar]
  139. 139. 
    Takahashi N, Coluccio A, Thorball CW, Planet E, Shi H et al. 2019. ZNF445 is a primary regulator of genomic imprinting. Genes Dev 33:49–54
    [Google Scholar]
  140. 140. 
    Quenneville S, Verde G, Corsinotti A, Kapopoulou A, Jakobsson J et al. 2011. In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions. Mol. Cell 44:361–72
    [Google Scholar]
  141. 141. 
    Sanchez-Delgado M, Court F, Vidal E, Medrano J, Monteagudo-Sanchez A et al. 2016. Human oocyte-derived methylation differences persist in the placenta revealing widespread transient imprinting. PLOS Genet 12:e1006427
    [Google Scholar]
  142. 142. 
    Hanna CW, Penaherrera MS, Saadeh H, Andrews S, McFadden DE et al. 2016. Pervasive polymorphic imprinted methylation in the human placenta. Genome Res 26:756–67
    [Google Scholar]
  143. 143. 
    Hamada H, Okae H, Toh H, Chiba H, Hiura H et al. 2016. Allele-specific methylome and transcriptome analysis reveals widespread imprinting in the human placenta. Am. J. Hum. Genet. 99:1045–58
    [Google Scholar]
  144. 144. 
    Smith ZD, Shi J, Gu H, Donaghey J, Clement K et al. 2017. Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer. Nature 549:543–47
    [Google Scholar]
  145. 145. 
    Guenatri M, Duffie R, Iranzo J, Fauque P, Bourc'his D 2013. Plasticity in Dnmt3L-dependent and -independent modes of de novo methylation in the developing mouse embryo. Development 140:562–72
    [Google Scholar]
  146. 146. 
    DaRosa PA, Harrison JS, Zelter A, Davis TN, Brzovic P et al. 2018. A bifunctional role for the UHRF1 UBL domain in the control of hemi-methylated DNA-dependent histone ubiquitylation. Mol. Cell 72:753–65.e6
    [Google Scholar]
  147. 147. 
    Foster BM, Stolz P, Mulholland CB, Montoya A, Kramer H et al. 2018. Critical role of the UBL domain in stimulating the E3 ubiquitin ligase activity of UHRF1 toward chromatin. Mol. Cell 72:739–52.e9
    [Google Scholar]
  148. 148. 
    Ferry L, Fournier A, Tsusaka T, Adelmant G, Shimazu T et al. 2017. Methylation of DNA Ligase 1 by G9a/GLP recruits UHRF1 to replicating DNA and regulates DNA methylation. Mol. Cell 67:550–65.e5
    [Google Scholar]
  149. 149. 
    Gelato KA, Tauber M, Ong MS, Winter S, Hiragami-Hamada K et al. 2014. Accessibility of different histone H3-binding domains of UHRF1 is allosterically regulated by phosphatidylinositol 5-phosphate. Mol. Cell 54:905–19
    [Google Scholar]
  150. 150. 
    Hanna CW, Taudt A, Huang J, Gahurova L, Kranz A et al. 2018. MLL2 conveys transcription-independent H3K4 trimethylation in oocytes. Nat. Struct. Mol. Biol. 25:73–82
    [Google Scholar]
/content/journals/10.1146/annurev-biochem-103019-102815
Loading
/content/journals/10.1146/annurev-biochem-103019-102815
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error