1932

Abstract

DNA methylation is a chemical modification that occurs predominantly on CG dinucleotides in mammalian genomes. However, recent studies have revealed that non-CG methylation (mCH) is abundant and nonrandomly distributed in the genomes of pluripotent cells and brain cells, and is present at lower levels in many other human cells and tissues. Surprisingly, mCH in pluripotent cells is distinct from that in brain cells in terms of sequence specificity and association with transcription, indicating the existence of different mCH pathways. In addition, several recent studies have begun to reveal the biological significance of mCH in diverse cellular processes. In reprogrammed somatic cells, mCH marks megabase-scale regions that have failed to revert to the pluripotent epigenetic state. In myocytes, promoter mCH accumulation is associated with the transcriptional response to environmental factors. In brain cells, mCH accumulates during the establishment of neural circuits and is associated with Rett syndrome. In this review, we summarize the current understanding of mCH and its possible functional consequences in different biological contexts.

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2015-08-24
2024-06-18
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Literature Cited

  1. Aberg KA, McClay JL, Nerella S, Clark S, Kumar G. 1.  et al. 2014. Methylome-wide association study of schizophrenia: identifying blood biomarker signatures of environmental insults. JAMA Psychiatry 71:255–64 [Google Scholar]
  2. Aoki A, Suetake I, Miyagawa J, Fujio T, Chijiwa T. 2.  et al. 2001. Enzymatic properties of de novo-type mouse DNA (cytosine-5) methyltransferases. Nucleic Acids Res. 29:3506–12 [Google Scholar]
  3. Arand J, Spieler D, Karius T, Branco MR, Meilinger D. 3.  et al. 2012. In vivo control of CpG and non-CpG DNA methylation by DNA methyltransferases. PLOS Genet. 8:e1002750 [Google Scholar]
  4. Barrès R, Kirchner H, Rasmussen M, Yan J, Kantor FR. 4.  et al. 2013. Weight loss after gastric bypass surgery in human obesity remodels promoter methylation. Cell Rep. 3:1020–27 [Google Scholar]
  5. Barrès R, Osler ME, Yan J, Rune A, Fritz T. 5.  et al. 2009. Non-CpG methylation of the PGC-1α promoter through DNMT3B controls mitochondrial density. Cell Metab. 10:189–98 [Google Scholar]
  6. Baubec T, Colombo DF, Wirbelauer C, Schmidt J, Burger L. 6.  et al. 2015. Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. Nature 520:243–47 [Google Scholar]
  7. Berman BP, Weisenberger DJ, Aman JF, Hinoue T, Ramjan Z. 7.  et al. 2012. Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Nat. Genet. 44:40–46 [Google Scholar]
  8. Bird A. 8.  2002. DNA methylation patterns and epigenetic memory. Genes Dev. 16:6–21 [Google Scholar]
  9. Bock C, Beerman I, Lien WH, Smith ZD, Gu H. 9.  et al. 2012. DNA methylation dynamics during in vivo differentiation of blood and skin stem cells. Mol. Cell 47:633–47 [Google Scholar]
  10. Bostick M, Kim JK, Esteve PO, Clark A, Pradhan S, Jacobsen SE. 10.  2007. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 317:1760–64 [Google Scholar]
  11. Boulard M, Edwards JR, Bestor TH. 11.  2015. FBXL10 protects Polycomb-bound genes from hypermethylation. Nat. Genet. 47:479–85 [Google Scholar]
  12. Bourc'his D, Xu GL, Lin CS, Bollman B, Bestor TH. 12.  2001. Dnmt3L and the establishment of maternal genomic imprints. Science 294:2536–39 [Google Scholar]
  13. Cedar H, Bergman Y. 13.  2009. Linking DNA methylation and histone modification: patterns and paradigms. Nat. Rev. Genet. 10:295–304 [Google Scholar]
  14. Chahrour M, Zoghbi HY. 14.  2007. The story of Rett syndrome: from clinic to neurobiology. Neuron 56:422–37 [Google Scholar]
  15. Chen L, Chen K, Lavery LA, Baker SA, Shaw CA. 15.  et al. 2015. MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome. PNAS 112:5509–14 [Google Scholar]
  16. Chen PY, Feng S, Joo JW, Jacobsen SE, Pellegrini M. 16.  2011. A comparative analysis of DNA methylation across human embryonic stem cell lines. Genome Biol. 12:R62 [Google Scholar]
  17. Chodavarapu RK, Feng S, Bernatavichute YV, Chen PY, Stroud H. 17.  et al. 2010. Relationship between nucleosome positioning and DNA methylation. Nature 466:388–92 [Google Scholar]
  18. Clowney EJ, LeGros MA, Mosley CP, Clowney FG, Markenskoff-Papadimitriou EC. 18.  et al. 2012. Nuclear aggregation of olfactory receptor genes governs their monogenic expression. Cell 151:724–37 [Google Scholar]
  19. Cokus SJ, Feng S, Zhang X, Chen Z, Merriman B. 19.  et al. 2008. Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 452:215–19 [Google Scholar]
  20. Dempster EL, Pidsley R, Schalkwyk LC, Owens S, Georgiades A. 20.  et al. 2011. Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Hum. Mol. Genet. 20:4786–96 [Google Scholar]
  21. Dhayalan A, Rajavelu A, Rathert P, Tamas R, Jurkowska RZ. 21.  et al. 2010. The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation. J. Biol. Chem. 285:26114–20 [Google Scholar]
  22. Doi A, Park IH, Wen B, Murakami P, Aryee MJ. 22.  et al. 2009. Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nat. Genet. 41:1350–53 [Google Scholar]
  23. Dyachenko OV, Schevchuk TV, Kretzner L, Buryanov YI, Smith SS. 23.  2010. Human non-CG methylation: Are human stem cells plant-like?. Epigenetics 5:569–72 [Google Scholar]
  24. Farlik M, Sheffield NC, Nuzzo A, Datlinger P, Schönegger A. 23a.  2015. Single-cell DNA methylome sequencing and bioinformatic inference of epigenomic cell-state dynamics. Cell Rep. 10:1386–97 [Google Scholar]
  25. Feng S, Cokus SJ, Zhang X, Chen PY, Bostick M. 24.  et al. 2010. Conservation and divergence of methylation patterning in plants and animals. PNAS 107:8689–94 [Google Scholar]
  26. Foret S, Kucharski R, Pellegrini M, Feng S, Jacobsen SE. 25.  et al. 2012. DNA methylation dynamics, metabolic fluxes, gene splicing, and alternative phenotypes in honey bees. PNAS 109:4968–73 [Google Scholar]
  27. Frommer M, McDonald LE, Millar DS, Collis CM, Watt F. 26.  et al. 1992. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. PNAS 89:1827–31 [Google Scholar]
  28. Gabel HW, Kinde B, Stroud H, Gilbert CS, Harmin DA. 27.  et al. 2015. Disruption of DNA-methylation-dependent long gene repression in Rett syndrome. Nature 52289–93 [Google Scholar]
  29. Gifford CA, Ziller MJ, Gu H, Trapnell C, Donaghey J. 28.  et al. 2013. Transcriptional and epigenetic dynamics during specification of human embryonic stem cells. Cell 153:1149–63 [Google Scholar]
  30. Gowher H, Jeltsch A. 28a.  2001. Enzymatic properties of recombinant Dnmt3a DNA methyltransferase from mouse: The enzyme modifies DNA in a non-processive manner and also methylates non-CpA sites. J. Mol. Biol 309:1201–8 [Google Scholar]
  31. Gowher H, Jeltsch A. 29.  2002. Molecular enzymology of the catalytic domains of the Dnmt3a and Dnmt3b DNA methyltransferases. J. Biol. Chem. 277:20409–14 [Google Scholar]
  32. Guo H, Zhu P, Wu X, Li X, Wen L, Tang F. 30.  2013. Single-cell methylome landscapes of mouse embryonic stem cells and early embryos analyzed using reduced representation bisulfite sequencing. Genome Res. 23:2126–35 [Google Scholar]
  33. Guo H, Zhu P, Yan L, Li R, Hu B. 31.  et al. 2014. The DNA methylation landscape of human early embryos. Nature 511:606–10 [Google Scholar]
  34. Guo JU, Su Y, Shin JH, Shin J, Li H. 32.  et al. 2014. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat. Neurosci. 17:215–22 [Google Scholar]
  35. Guo JU, Su Y, Zhong C, Ming GL, Song H. 33.  2011. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145:423–34 [Google Scholar]
  36. Guo W, Chung WY, Qian M, Pellegrini M, Zhang MQ. 34.  2014. Characterizing the strand-specific distribution of non-CpG methylation in human pluripotent cells. Nucleic Acids Res. 42:3009–16 [Google Scholar]
  37. Guo X, Wang L, Li J, Ding Z, Xiao J. 35.  et al. 2014. Structural insight into autoinhibition and histone H3-induced activation of DNMT3A. Nature 517:640–44 [Google Scholar]
  38. Guy J, Cheval H, Selfridge J, Bird A. 36.  2011. The role of MeCP2 in the brain. Annu. Rev. Cell Dev. Biol. 27:631–52 [Google Scholar]
  39. Haines TR, Rodenhiser DI, Ainsworth PJ. 37.  2001. Allele-specific non-CpG methylation of the Nf1 gene during early mouse development. Dev. Biol. 240:585–98 [Google Scholar]
  40. Hansen DV, Lui JH, Flandin P, Yoshikawa K, Rubenstein JL. 38.  et al. 2013. Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences. Nat. Neurosci. 16:1576–87 [Google Scholar]
  41. Hata K, Okano M, Lei H, Li E. 39.  2002. Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development 129:1983–93 [Google Scholar]
  42. Holz-Schietinger C, Reich NO. 40.  2010. The inherent processivity of the human de novo methyltransferase 3A (DNMT3A) is enhanced by DNMT3L. J. Biol. Chem. 285:29091–100 [Google Scholar]
  43. Hovestadt V, Jones DT, Picelli S, Wang W, Kool M. 41.  et al. 2014. Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing. Nature 510:537–41 [Google Scholar]
  44. Hu L, Li Z, Cheng J, Rao Q, Gong W. 42.  et al. 2013. Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation. Cell 155:1545–55 [Google Scholar]
  45. Ichiyanagi T, Ichiyanagi K, Miyake M, Sasaki H. 43.  2013. Accumulation and loss of asymmetric non-CpG methylation during male germ-cell development. Nucleic Acids Res. 41:738–45 [Google Scholar]
  46. Inoue S, Oishi M. 44.  2005. Effects of methylation of non-CpG sequence in the promoter region on the expression of human synaptotagmin XI (syt11). Gene 348:123–34 [Google Scholar]
  47. Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C. 45.  et al. 2009. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat. Genet. 41:178–86 [Google Scholar]
  48. Jia D, Jurkowska RZ, Zhang X, Jeltsch A, Cheng X. 46.  2007. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature 449:248–51 [Google Scholar]
  49. Jones PA. 47.  2012. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13:484–92 [Google Scholar]
  50. Laurent L, Wong E, Li G, Huynh T, Tsirigos A. 48.  et al. 2010. Dynamic changes in the human methylome during differentiation. Genome Res. 20:320–31 [Google Scholar]
  51. Law JA, Jacobsen SE. 49.  2010. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat. Rev. Genet. 11:204–20 [Google Scholar]
  52. Lazarovici A, Zhou T, Shafer A, Dantas Machado AC, Riley TR. 50.  et al. 2013. Probing DNA shape and methylation state on a genomic scale with DNase I. PNAS 110:6376–81 [Google Scholar]
  53. Li Y, Wang H, Muffat J, Cheng AW, Orlando DA. 51.  et al. 2013. Global transcriptional and translational repression in human-embryonic-stem-cell-derived Rett syndrome neurons. Cell Stem Cell 13:446–58 [Google Scholar]
  54. Liao J, Karnik R, Gu H, Ziller MJ, Clement K. 52.  et al. 2015. Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells. Nat. Genet. 47:469–78 [Google Scholar]
  55. Ling C, Groop L. 53.  2009. Epigenetics: a molecular link between environmental factors and type 2 diabetes. Diabetes 58:2718–25 [Google Scholar]
  56. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA. 54.  et al. 2013. Global epigenomic reconfiguration during mammalian brain development. Science 341:1237905 [Google Scholar]
  57. Lister R, O'Malley RC, Tonti-Filippini J, Gregory BD, Berry CC. 55.  et al. 2008. Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell 133:523–36 [Google Scholar]
  58. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G. 56.  et al. 2009. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462:315–22 [Google Scholar]
  59. Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR. 57.  et al. 2011. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471:68–73 [Google Scholar]
  60. Liu Y, Aryee MJ, Padyukov L, Fallin MD, Hesselberg E. 58.  et al. 2013. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat. Biotechnol. 31:142–47 [Google Scholar]
  61. Lodwick D, Ross HN, Harris JE, Almond JW, Grant WD. 59.  1986. dam methylation in the Archaebacteria. J. Gen. Microbiol. 132:3055–59 [Google Scholar]
  62. Lomvardas S, Barnea G, Pisapia DJ, Mendelsohn M, Kirkland J, Axel R. 60.  2006. Interchromosomal interactions and olfactory receptor choice. Cell 126:403–13 [Google Scholar]
  63. Ma H, Morey R, O'Neil RC, He Y, Daughtry B. 61.  et al. 2014. Abnormalities in human pluripotent cells due to reprogramming mechanisms. Nature 511:177–83 [Google Scholar]
  64. Magklara A, Yen A, Colquitt BM, Clowney EJ, Allen W. 62.  et al. 2011. An epigenetic signature for monoallelic olfactory receptor expression. Cell 145:555–70 [Google Scholar]
  65. Meissner A. 63.  2010. Epigenetic modifications in pluripotent and differentiated cells. Nat. Biotechnol. 28:1079–88 [Google Scholar]
  66. Meissner A, Gnirke A, Bell GW, Ramsahoye B, Lander ES, Jaenisch R. 64.  2005. Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis. Nucleic Acids Res. 33:5868–77 [Google Scholar]
  67. Metzker ML. 65.  2010. Sequencing technologies—the next generation. Nat. Rev. Genet. 11:31–46 [Google Scholar]
  68. Mill J, Tang T, Kaminsky Z, Khare T, Yazdanpanah S. 66.  et al. 2008. Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am. J. Hum. Genet. 82:696–711 [Google Scholar]
  69. Nan X, Campoy FJ, Bird A. 67.  1997. MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell 88:471–81 [Google Scholar]
  70. Nguyen S, Meletis K, Fu D, Jhaveri S, Jaenisch R. 68.  2007. Ablation of de novo DNA methyltransferase Dnmt3a in the nervous system leads to neuromuscular defects and shortened lifespan. Dev. Dyn. 236:1663–76 [Google Scholar]
  71. Ooi SKT, Qiu C, Bernstein E, Li K, Jia D. 69.  et al. 2007. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448:714–17 [Google Scholar]
  72. Otani J, Nankumo T, Arita K, Inamoto S, Ariyoshi M, Shirakawa M. 70.  2009. Structural basis for recognition of H3K4 methylation status by the DNA methyltransferase 3A ATRX-DNMT3-DNMT3L domain. EMBO Rep. 10:1235–41 [Google Scholar]
  73. Patil V, Ward RL, Hesson LB. 71.  2014. The evidence for functional non-CpG methylation in mammalian cells. Epigenetics 9:823–28 [Google Scholar]
  74. Peoples OP, Hardman N. 72.  1983. An abundant family of methylated repetitive sequences dominates the genome of Physarum polycephalum. Nucleic Acids Res. 11:7777–88 [Google Scholar]
  75. Pidsley R, Viana J, Hannon E, Spiers HH, Troakes C. 73.  et al. 2014. Methylomic profiling of human brain tissue supports a neurodevelopmental origin for schizophrenia. Genome Biol. 15:483 [Google Scholar]
  76. Pinney SE. 74.  2014. Mammalian non-CpG methylation: stem cells and beyond. Biology 3:739–51 [Google Scholar]
  77. Plongthongkum N, Diep DH, Zhang K. 75.  2014. Advances in the profiling of DNA modifications: cytosine methylation and beyond. Nat. Rev. Genet. 15:647–61 [Google Scholar]
  78. Ramsahoye BH, Biniszkiewicz D, Lyko F, Clark V, Bird AP, Jaenisch R. 76.  2000. Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. PNAS 97:5237–42 [Google Scholar]
  79. Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A. 77.  2000. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat. Biotechnol. 18:399–404 [Google Scholar]
  80. Riggs AD. 78.  1975. X inactivation, differentiation, and DNA methylation. Cytogenet. Cell Genet. 14:9–25 [Google Scholar]
  81. Riggs AD. 79.  2002. X chromosome inactivation, differentiation, and DNA methylation revisited, with a tribute to Susumu Ohno. Cytogenet. Genome Res. 99:17–24 [Google Scholar]
  82. Sasaki H, Matsui Y. 80.  2008. Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat. Rev. Genet. 9:129–40 [Google Scholar]
  83. Schmitz RJ, He Y, Valdes-Lopez O, Khan SM, Joshi T. 81.  et al. 2013. Epigenome-wide inheritance of cytosine methylation variants in a recombinant inbred population. Genome Res. 23:1663–74 [Google Scholar]
  84. Schultz MD, He Y, Whitaker JW, Hariharan M, Mukamel EA. 82.  et al. 2015. Human body epigenome maps reveal noncanonical DNA methylation variation. Nature. In press. doi: 10.1038/nature14465 [Google Scholar]
  85. Schultz MD, Schmitz RJ, Ecker JR. 83.  2012. “Leveling” the playing field for analyses of single-base resolution DNA methylomes. Trends Genet. 28:583–85 [Google Scholar]
  86. Shahbazian MD, Antalffy B, Armstrong DL, Zoghbi HY. 84.  2002. Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation. Hum. Mol. Genet. 11:115–24 [Google Scholar]
  87. Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A. 85.  et al. 2007. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature 450:908–12 [Google Scholar]
  88. Shin J, Ming GL, Song H. 86.  2014. DNA modifications in the mammalian brain. Philos. Trans. R. Soc. B 369:20130512 [Google Scholar]
  89. Shirane K, Toh H, Kobayashi H, Miura F, Chiba H. 87.  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]
  90. Skene PJ, Illingworth RS, Webb S, Kerr AR, James KD. 88.  et al. 2010. Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state. Mol. Cell 37:457–68 [Google Scholar]
  91. Smallwood SA, Lee HJ, Angermueller C, Krueger F, Saadeh H. 89.  et al. 2014. Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Nat. Methods 11:817–20 [Google Scholar]
  92. Smith ZD, Meissner A. 90.  2013. DNA methylation: roles in mammalian development. Nat. Rev. Genet. 14:204–20 [Google Scholar]
  93. Stadler MB, Murr R, Burger L, Ivanek R, Lienert F. 91.  et al. 2011. DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature 480:490–95 [Google Scholar]
  94. Suetake I, Miyazaki J, Murakami C, Takeshima H, Tajima S. 92.  2003. Distinct enzymatic properties of recombinant mouse DNA methyltransferases Dnmt3a and Dnmt3b. J. Biochem. 133:737–44 [Google Scholar]
  95. Suetake I, Shinozaki F, Miyagawa J, Takeshima H, Tajima S. 93.  2004. DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. J. Biol. Chem. 279:27816–23 [Google Scholar]
  96. Tachibana M, Amato P, Sparman M, Gutierrez NM, Tippner-Hedges R. 94.  et al. 2013. Human embryonic stem cells derived by somatic cell nuclear transfer. Cell 153:1228–38 [Google Scholar]
  97. Takahashi K, Yamanaka S. 95.  2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–76 [Google Scholar]
  98. Tiedemann RL, Putiri EL, Lee J-H, Hlady RA, Kashiwagi K. 96.  et al. 2014. Acute depletion redefines the division of labor among DNA methyltransferases in methylating the human genome. Cell Rep. 9:1554–66 [Google Scholar]
  99. Tomizawa S, Kobayashi H, Watanabe T, Andrews S, Hata K. 97.  et al. 2011. Dynamic stage-specific changes in imprinted differentially methylated regions during early mammalian development and prevalence of non-CpG methylation in oocytes. Development 138:811–20 [Google Scholar]
  100. Varley KE, Gertz J, Bowling KM, Parker SL, Reddy TE. 98.  et al. 2013. Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res. 23:555–67 [Google Scholar]
  101. Vettermann C, Schlissel MS. 99.  2010. Allelic exclusion of immunoglobulin genes: models and mechanisms. Immunol. Rev. 237:22–42 [Google Scholar]
  102. Vlachogiannis G, Niederhuth CE, Tuna S, Stathopoulou A, Viiri K. 100.  et al. 2015. The Dnmt3L ADD domain controls cytosine methylation establishment during spermatogenesis. Cell Rep. 10:944–56 [Google Scholar]
  103. Wang L, Zhang J, Duan J, Gao X, Zhu W. 101.  et al. 2014. Programming and inheritance of parental DNA methylomes in mammals. Cell 157:979–91 [Google Scholar]
  104. Wilson GG, Murray NE. 102.  1991. Restriction and modification systems. Annu. Rev. Genet. 25:585–627 [Google Scholar]
  105. Wu H, Zhang Y. 103.  2014. Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell 156:45–68 [Google Scholar]
  106. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G. 104.  et al. 1999. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–24 [Google Scholar]
  107. Xie W, Barr CL, Kim A, Yue F, Lee AY. 105.  et al. 2012. Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome. Cell 148:816–31 [Google Scholar]
  108. Xie W, Schultz MD, Lister R, Hou Z, Rajagopal N. 106.  et al. 2013. Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell 153:1134–48 [Google Scholar]
  109. Yu M, Hon GC, Szulwach KE, Song CX, Zhang L. 107.  et al. 2012. Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome. Cell 149:1368–80 [Google Scholar]
  110. Zemach A, McDaniel IE, Silva P, Zilberman D. 108.  2010. Genome-wide evolutionary analysis of eukaryotic DNA methylation. Science 328:916–19 [Google Scholar]
  111. Zhang SC, Wernig M, Duncan ID, Brustle O, Thomson JA. 109.  2001. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat. Biotechnol. 19:1129–33 [Google Scholar]
  112. Zhang X, Yazaki J, Sundaresan A, Cokus S, Chan SW. 110.  et al. 2006. Genome-wide high-resolution mapping and functional analysis of DNA methylation in Arabidopsis. Cell 126:1189–201 [Google Scholar]
  113. Zhu J, Adli M, Zou JY, Verstappen G, Coyne M. 111.  et al. 2013. Genome-wide chromatin state transitions associated with developmental and environmental cues. Cell 152:642–54 [Google Scholar]
  114. Ziller MJ, Gu H, Muller F, Donaghey J, Tsai LT. 112.  et al. 2013. Charting a dynamic DNA methylation landscape of the human genome. Nature 500:477–81 [Google Scholar]
  115. Ziller MJ, Muller F, Liao J, Zhang Y, Gu H. 113.  et al. 2011. Genomic distribution and inter-sample variation of non-CpG methylation across human cell types. PLOS Genet. 7:e1002389 [Google Scholar]
  116. Zvetkova I, Apedaile A, Ramsahoye B, Mermoud JE, Crompton LA. 114.  et al. 2005. Global hypomethylation of the genome in XX embryonic stem cells. Nat. Genet. 37:1274–79 [Google Scholar]
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