DNA Methylation in Eukaryotes: Regulation and Function

  • Hans Helmut Niller
  • Anett Demcsák
  • Janos Minarovits
Reference work entry
Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (HHLM)


In this chapter we focus on the regulation and function of DNA methylation in mammals and especially in humans. We describe the main features of the enzymatic machinery generating 5-methylcytosine (5mC) that functions as an epigenetic mark in mammalian cells, and outline the active and passive mechanisms that can remove this reversible modification of DNA. We briefly introduce the characteristics of “maintenance” and “de novo” DNA-(cytosine-C5)-methyltransferases (DNMTs) and overview how their expression is regulated at the transcriptional, posttranscriptional, and posttranslational level. The interacting partners and chromatin marks involved in the targeting of DNMTs to the replication foci during S phase or to various chromatin domains during other phases of the cell cycle are also discussed. The enzymatic functions of DNMTs and their interactions with cellular macromolecules are involved in a series of cellular processes, some of them vital for mammals. Thus, DNA methylation has a role in the regulation of chromatin structure and promoter activity. It may silence the promoters of imprinted genes showing monoallelic expression as well as the promoters of transposons, and contributes to gene silencing on the inactive X chromosome, too. There are genome-wide demethylation and remethylation events during embryogenesis suggesting a regulatory role for DNA methylation in developmental processes, and both cytosine methylation and the active removal of 5mC from DNA is involved in the control of cell differentiation. DNA methylation plays a role in the preservation of genomic stability and gene body methylation affects the inclusion of certain exons into mature mRNA molecules by affecting – indirectly – the splicing of primary transcripts. Epigenetic regulatory mechanisms, including DNA methylation, are at the forefront of brain research these days. For this reason we outlined some of the most interesting results of this exciting new field in a separate subsection.



This work was supported by the grant GINOP-2.3.2-15-2016-00011 to a consortium led by the University of Szeged, Szeged, Hungary (participants: the University of Debrecen, Debrecen, and the Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary), project leader Janos Minarovits. The grant was funded by the European Regional Development Fund of the European Union and managed in the framework of Economic Development and Innovation Operational Programme by the Ministry of National Economy, National Research, Development and Innovation Office, Budapest, Hungary.


  1. Adhikari S, Curtis PD (2016) DNA methyltransferases and epigenetic regulation in bacteria. FEMS Microbiol Rev 40:575–591PubMedCrossRefGoogle Scholar
  2. Alelu-Paz R, Carmona FJ, Sanchez-Mut JV, Cariaga-Martinez A, Gonzalez-Corpas A, Ashour N, Orea MJ, Escanilla A, Monje A, Guerrero Marquez C, Saiz-Ruiz J, Esteller M, Ropero S (2016) Epigenetics in schizophrenia: a pilot study of global DNA methylation in different brain regions associated with higher cognitive functions. Front Psychol 7:1496PubMedPubMedCentralCrossRefGoogle Scholar
  3. Amouroux R, Nashun B, Shirane K, Nakagawa S, Hill PW, D’souza Z, Nakayama M, Matsuda M, Turp A, Ndjetehe E, Encheva V, Kudo NR, Koseki H, Sasaki H, Hajkova P (2016) De novo DNA methylation drives 5hmC accumulation in mouse zygotes. Nat Cell Biol 18:225–233PubMedPubMedCentralCrossRefGoogle Scholar
  4. Anacker C, O’Donnell KJ, Meaney MJ (2014) Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function. Dialogues Clin Neurosci 16:321–333PubMedPubMedCentralGoogle Scholar
  5. Angermueller C, Clark SJ, Lee HJ, Macaulay IC, Teng MJ, Hu TX, Krueger F, Smallwood SA, Ponting CP, Voet T, Kelsey G, Stegle O, Reik W (2016) Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity. Nat Methods 13:229–232PubMedPubMedCentralCrossRefGoogle Scholar
  6. Aran D, Sabato S, Hellman A (2013) DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes. Genome Biol 14:R21PubMedPubMedCentralCrossRefGoogle Scholar
  7. Ardissone S, Redder P, Russo G, Frandi A, Fumeaux C, Patrignani A, Schlapbach R, Falquet L, Viollier PH (2016) Cell cycle constraints and environmental control of local DNA Hypomethylation in alpha-Proteobacteria. PLoS Genet 12:e1006499PubMedPubMedCentralCrossRefGoogle Scholar
  8. Athanasiadou R, De Sousa D, Myant K, Merusi C, Stancheva I, Bird A (2010) Targeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells. PLoS One 5:e9937PubMedPubMedCentralCrossRefGoogle Scholar
  9. Ay E, Banati F, Mezei M, Bakos A, Niller HH, Buzas K, Minarovits J (2013) Epigenetics of HIV infection: promising research areas and implications for therapy. AIDS Rev 15:181–188PubMedGoogle Scholar
  10. Bahar Halpern K, Vana T, Walker MD (2014) Paradoxical role of DNA methylation in activation of FoxA2 gene expression during endoderm development. J Biol Chem 289:23882–23892PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bala Tannan N, Brahmachary M, Garg P, Borel C, Alnefaie R, Watson CT, Thomas NS, Sharp AJ (2014) DNA methylation profiling in X;autosome translocations supports a role for L1 repeats in the spread of X chromosome inactivation. Hum Mol Genet 23:1224–1236PubMedCrossRefGoogle Scholar
  12. Bale TL (2015) Epigenetic and transgenerational reprogramming of brain development. Nat Rev Neurosci 16:332–344PubMedCrossRefGoogle Scholar
  13. Barlow DP, Bartolomei MS (2014) Genomic imprinting in mammals. Cold Spring Harb Perspect Biol 6:a018382Google Scholar
  14. Bartolomei MS, Ferguson-Smith AC (2011) Mammalian genomic imprinting. Cold Spring Harb Perspect Biol 3:a002592Google Scholar
  15. Becker C, Hagmann J, Muller J, Koenig D, Stegle O, Borgwardt K, Weigel D (2011) Spontaneous epigenetic variation in the Arabidopsis thaliana methylome. Nature 480:245–249PubMedCrossRefGoogle Scholar
  16. Bell AC, Felsenfeld G (2000) Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf 2 gene. Nature 405:482–485PubMedCrossRefGoogle Scholar
  17. Bell CG, Wilson GA, Beck S (2014) Human-specific CpG ‘beacons’ identify human-specific prefrontal cortex H3K4me3 chromatin peaks. Epigenomics 6:21–31PubMedCrossRefGoogle Scholar
  18. Bell CG, Wilson GA, Butcher LM, Roos C, Walter L, Beck S (2012) Human-specific CpG ‘beacons’ identify loci associated with human-specific traits and disease. Epigenetics 7:1188–1199PubMedPubMedCentralCrossRefGoogle Scholar
  19. Berchtold NC, Sabbagh MN, Beach TG, Kim RC, Cribbs DH, Cotman CW (2014) Brain gene expression patterns differentiate mild cognitive impairment from normal aged and Alzheimer’s disease. Neurobiol Aging 35:1961–1972PubMedPubMedCentralCrossRefGoogle Scholar
  20. Berkyurek AC, Suetake I, Arita K, Takeshita K, Nakagawa A, Shirakawa M, Tajima S (2014) The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA. J Biol Chem 289:379–386PubMedCrossRefGoogle Scholar
  21. Bestor TH (1990) DNA methylation: evolution of a bacterial immune function into a regulator of gene expression and genome structure in higher eukaryotes. Philos Trans R Soc Lond Ser B Biol Sci 326:179–187CrossRefGoogle Scholar
  22. Bestor TH (2000) The DNA methyltransferases of mammals. Hum Mol Genet 9:2395–2402PubMedCrossRefGoogle Scholar
  23. Bestor TH, Edwards JR, Boulard M (2015) Notes on the role of dynamic DNA methylation in mammalian development. Proc Natl Acad Sci U S A 112:6796–6799PubMedCrossRefGoogle Scholar
  24. Bheemanaik S, Reddy YV, Rao DN (2006) Structure, function and mechanism of exocyclic DNA methyltransferases. Biochem J 399:177–190PubMedPubMedCentralCrossRefGoogle Scholar
  25. Bhende PM, Seaman WT, Delecluse HJ, Kenney SC (2004) The EBV lytic switch protein, Z, preferentially binds to and activates the methylated viral genome. Nat Genet 36:1099–1104PubMedCrossRefGoogle Scholar
  26. Bianchi C, Zangi R (2014) Dual base-flipping of cytosines in a CpG dinucleotide sequence. Biophys Chem 187-188:14–22PubMedCrossRefGoogle Scholar
  27. Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21PubMedCrossRefGoogle Scholar
  28. Bird AP (1986) CpG-rich islands and the function of DNA methylation. Nature 321:209–213PubMedCrossRefGoogle Scholar
  29. Bird AP (1987) CpG islands as gene markers in the vertebrate nucleus. Trends Genet 3:342–347CrossRefGoogle Scholar
  30. Blattler A, Farnham PJ (2013) Cross-talk between site-specific transcription factors and DNA methylation states. J Biol Chem 288:34287–34294PubMedPubMedCentralCrossRefGoogle Scholar
  31. Blow MJ, Clark TA, Daum CG, Deutschbauer AM, Fomenkov A, Fries R, Froula J, Kang DD, Malmstrom RR, Morgan RD, Posfai J, Singh K, Visel A, Wetmore K, Zhao Z, Rubin EM, Korlach J, Pennacchio LA, Roberts RJ (2016) The epigenomic landscape of prokaryotes. PLoS Genet 12:e1005854PubMedPubMedCentralCrossRefGoogle Scholar
  32. Bogdanovic O, Veenstra GJ (2009) DNA methylation and methyl-CpG binding proteins: developmental requirements and function. Chromosoma 118:549–565PubMedPubMedCentralCrossRefGoogle Scholar
  33. Bohacek J, Mansuy IM (2015) Molecular insights into transgenerational non-genetic inheritance of acquired behaviours. Nat Rev Genet 16:641–652PubMedCrossRefGoogle Scholar
  34. Braidotti G, Baubec T, Pauler F, Seidl C, Smrzka O, Stricker S, Yotova I, Barlow DP (2004) The air noncoding RNA: an imprinted cis-silencing transcript. Cold Spring Harb Symp Quant Biol 69:55–66PubMedPubMedCentralCrossRefGoogle Scholar
  35. Brockdorff N (2013) Noncoding RNA and Polycomb recruitment. RNA 19:429–442PubMedPubMedCentralCrossRefGoogle Scholar
  36. Brockdorff N, Turner BM (2015) Dosage compensation in mammals. Cold Spring Harb Perspect Biol 7:a019406PubMedPubMedCentralCrossRefGoogle Scholar
  37. Calfa G, Percy AK, Pozzo-Miller L (2012) Dysfunction of methyl-CpG-binding protein MeCP2 in Rett syndrome. In: Minarovits J, Niller HH (eds) Patho-epigenetics of disease. Springer, New York, pp 43–69CrossRefGoogle Scholar
  38. Cano-Rodriguez D, Rots MG (2016) Epigenetic editing: on the verge of reprogramming gene expression at will. Curr Genet Med Rep 4:170–179PubMedPubMedCentralCrossRefGoogle Scholar
  39. Casadesus J (2016) Bacterial DNA methylation and Methylomes. Adv Exp Med Biol 945:35–61PubMedCrossRefGoogle Scholar
  40. Centeno TP, Shomroni O, Hennion M, Halder R, Vidal R, Rahman RU, Bonn S (2016) Genome-wide chromatin and gene expression profiling during memory formation and maintenance in adult mice. Sci Data 3:160090PubMedPubMedCentralCrossRefGoogle Scholar
  41. Cerase A, Pintacuda G, Tattermusch A, Avner P (2015) Xist localization and function: new insights from multiple levels. Genome Biol 16:166PubMedPubMedCentralCrossRefGoogle Scholar
  42. Chaligne R, Heard E (2014) X-chromosome inactivation in development and cancer. FEBS Lett 588:2514–2522PubMedCrossRefGoogle Scholar
  43. Champagne FA, Curley JP (2009) Epigenetic mechanisms mediating the long-term effects of maternal care on development. Neurosci Biobehav Rev 33:593–600PubMedCrossRefGoogle Scholar
  44. Chen BF, Chan WY (2014) The de novo DNA methyltransferase DNMT3A in development and cancer. Epigenetics 9:669–677PubMedPubMedCentralCrossRefGoogle Scholar
  45. Chen CK, Blanco M, Jackson C, Aznauryan E, Ollikainen N, Surka C, Chow A, Cerase A, McDonel P, Guttman M (2016a) Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing. Science 354:468–472PubMedCrossRefGoogle Scholar
  46. Chen Q, Yan M, Cao Z, Li X, Zhang Y, Shi J, Feng GH, Peng H, Zhang X, Zhang Y, Qian J, Duan E, Zhai Q, Zhou Q (2016b) Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science 351:397–400PubMedCrossRefGoogle Scholar
  47. Chen Q, Yan W, Duan E (2016c) Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications. Nat Rev Genet 17:733–743PubMedPubMedCentralCrossRefGoogle Scholar
  48. Chen, R., Zhang, Q., Duan, X., York, P., Chen, G.D., Yin, P., Zhu, H., Xu, M., Chen, P., Wu, Q., Li, D., Samarut, J., Xu, G., Zhang, P., Cao, X., Li, J., and Wong, J. (2017). The 5-hydroxymethylcytosine (5hmC) reader Uhrf2 is required for normal levels of 5hmC in mouse adult brain and spatial learning and memory. J Biol Chem.Google Scholar
  49. 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 24:9048–9058PubMedPubMedCentralCrossRefGoogle Scholar
  50. Chen Y, Damayanti NP, Irudayaraj J, Dunn K, Zhou FC (2014) Diversity of two forms of DNA methylation in the brain. Front Genet 5:46PubMedPubMedCentralGoogle Scholar
  51. Cheng X, Blumenthal RM (2011) Introduction--epiphanies in epigenetics. Prog Mol Biol Transl Sci 101:1–21PubMedPubMedCentralCrossRefGoogle Scholar
  52. Cheng Y, Bernstein A, Chen D, Jin P (2015) 5-Hydroxymethylcytosine: a new player in brain disorders? Exp Neurol 268:3–9PubMedCrossRefGoogle Scholar
  53. Chestnut BA, Chang Q, Price A, Lesuisse C, Wong M, Martin LJ (2011) Epigenetic regulation of motor neuron cell death through DNA methylation. J Neurosci 31:16619–16636PubMedPubMedCentralCrossRefGoogle Scholar
  54. Choi SH, Heo K, Byun HM, An W, Lu W, Yang AS (2011) Identification of preferential target sites for human DNA methyltransferases. Nucleic Acids Res 39:104–118PubMedCrossRefGoogle Scholar
  55. Clark AT (2015) DNA methylation remodeling in vitro and in vivo. Curr Opin Genet Dev 34:82–87PubMedPubMedCentralCrossRefGoogle Scholar
  56. Cohen NR, Ross CA, Jain S, Shapiro RS, Gutierrez A, Belenky P, Li H, Collins JJ (2016) A role for the bacterial GATC methylome in antibiotic stress survival. Nat Genet 48:581–586PubMedPubMedCentralCrossRefGoogle Scholar
  57. Colot V, Rossignol JL (1999) Eukaryotic DNA methylation as an evolutionary device. BioEssays 21:402–411PubMedCrossRefGoogle Scholar
  58. Cooper DN, Mort M, Stenson PD, Ball EV, Chuzhanova NA (2010) Methylation-mediated deamination of 5-methylcytosine appears to give rise to mutations causing human inherited disease in CpNpG trinucleotides, as well as in CpG dinucleotides. Hum Genomics 4:406–410PubMedPubMedCentralCrossRefGoogle Scholar
  59. Csankovszki G, Nagy A, Jaenisch R (2001) Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation. J Cell Biol 153:773–784PubMedPubMedCentralCrossRefGoogle Scholar
  60. Dabe EC, Sanford RS, Kohn AB, Bobkova Y, Moroz LL (2015) DNA methylation in basal metazoans: insights from ctenophores. Integr Comp Biol 55:1096–1110PubMedPubMedCentralCrossRefGoogle Scholar
  61. Damelin M, Bestor TH (2007) Biological functions of DNA methyltransferase 1 require its methyltransferase activity. Mol Cell Biol 27:3891–3899PubMedPubMedCentralCrossRefGoogle Scholar
  62. Dan J, Chen T (2016) Genetic studies on mammalian DNA methyltransferases. Adv Exp Med Biol 945:123–150PubMedCrossRefGoogle Scholar
  63. Davies MN, Volta M, Pidsley R, Lunnon K, Dixit A, Lovestone S, Coarfa C, Harris RA, Milosavljevic A, Troakes C, Al-Sarraj S, Dobson R, Schalkwyk LC, Mill J (2012) Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biol 13:R43PubMedPubMedCentralCrossRefGoogle Scholar
  64. Davis HP, Squire LR (1984) Protein synthesis and memory: a review. Psychol Bull 96:518–559PubMedCrossRefGoogle Scholar
  65. Dawlaty MM, Breiling A, Le T, Barrasa MI, Raddatz G, Gao Q, Powell BE, Cheng AW, Faull KF, Lyko F, Jaenisch R (2014) Loss of Tet enzymes compromises proper differentiation of embryonic stem cells. Dev Cell 29:102–111PubMedPubMedCentralCrossRefGoogle Scholar
  66. De Larco JE, Wuertz BR, Yee D, Rickert BL, Furcht LT (2003) Atypical methylation of the interleukin-8 gene correlates strongly with the metastatic potential of breast carcinoma cells. Proc Natl Acad Sci U S A 100:13988–13993PubMedPubMedCentralCrossRefGoogle Scholar
  67. Dean W (2014) DNA methylation and demethylation: a pathway to gametogenesis and development. Mol Reprod Dev 81:113–125PubMedCrossRefGoogle Scholar
  68. Deaton AM, Bird A (2011) CpG islands and the regulation of transcription. Genes Dev 25:1010–1022PubMedPubMedCentralCrossRefGoogle Scholar
  69. Dekker AD, De Deyn PP, Rots MG (2014) Epigenetics: the neglected key to minimize learning and memory deficits in down syndrome. Neurosci Biobehav Rev 45:72–84PubMedCrossRefGoogle Scholar
  70. Delatte B, Deplus R, Fuks F (2014) Playing TETris with DNA modifications. EMBO J 33:1198–1211PubMedPubMedCentralGoogle Scholar
  71. Delgado-Morales R, Esteller M (2017) Opening up the DNA methylome of dementia. Mol Psychiatry 22:485–496.
  72. Denis H, Ndlovu MN, Fuks F (2011) Regulation of mammalian DNA methyltransferases: a route to new mechanisms. EMBO Rep 12:647–656PubMedPubMedCentralCrossRefGoogle Scholar
  73. Deplus R, Blanchon L, Rajavelu A, Boukaba A, Defrance M, Luciani J, Rothe F, Dedeurwaerder S, Denis H, Brinkman AB, Simmer F, Muller F, Bertin B, Berdasco M, Putmans P, Calonne E, Litchfield DW, De Launoit Y, Jurkowski TP, Stunnenberg HG, Bock C, Sotiriou C, Fraga MF, Esteller M, Jeltsch A, Fuks F (2014a) Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a. Cell Rep 8:743–753PubMedCrossRefGoogle Scholar
  74. Deplus R, Delatte B, Schwinn MK, Defrance M, Mendez J, Murphy N, Dawson MA, Volkmar M, Putmans P, Calonne E, Shih AH, Levine RL, Bernard O, Mercher T, Solary E, Urh M, Daniels DL, Fuks F (2013) TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J 32:645–655PubMedPubMedCentralCrossRefGoogle Scholar
  75. Deplus R, Denis H, Putmans P, Calonne E, Fourrez M, Yamamoto K, Suzuki A, Fuks F (2014b) Citrullination of DNMT3A by PADI4 regulates its stability and controls DNA methylation. Nucleic Acids Res 42:8285–8296PubMedPubMedCentralCrossRefGoogle Scholar
  76. Dhayalan A, Rajavelu A, Rathert P, Tamas R, Jurkowska RZ, Ragozin S, Jeltsch A (2010) The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation. J Biol Chem 285:26114–26120PubMedPubMedCentralCrossRefGoogle Scholar
  77. Dhayalan A, Tamas R, Bock I, Tattermusch A, Dimitrova E, Kudithipudi S, Ragozin S, Jeltsch A (2011) The ATRX-ADD domain binds to H3 tail peptides and reads the combined methylation state of K4 and K9. Hum Mol Genet 20:2195–2203PubMedPubMedCentralCrossRefGoogle Scholar
  78. Dias BG, Ressler KJ (2014) Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci 17:89–96PubMedCrossRefGoogle Scholar
  79. Du Q, Wang Z, Schramm VL (2016) Human DNMT1 transition state structure. Proc Natl Acad Sci U S A 113:2916–2921PubMedPubMedCentralCrossRefGoogle Scholar
  80. 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 7:11453PubMedPubMedCentralCrossRefGoogle Scholar
  81. Easwaran HP, Schermelleh L, Leonhardt H, Cardoso MC (2004) Replication-independent chromatin loading of Dnmt1 during G2 and M phases. EMBO Rep 5:1181–1186PubMedPubMedCentralCrossRefGoogle Scholar
  82. Eden A, Gaudet F, Waghmare A, Jaenisch R (2003) Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300:455PubMedCrossRefGoogle Scholar
  83. Edwards CA, Rens W, Clarke O, Mungall AJ, Hore T, Graves JA, Dunham I, Ferguson-Smith AC, Ferguson-Smith MA (2007) The evolution of imprinting: chromosomal mapping of orthologues of mammalian imprinted domains in monotreme and marsupial mammals. BMC Evol Biol 7:157PubMedPubMedCentralCrossRefGoogle Scholar
  84. Eggermann T (2012) Imprinting disorders. In: Minarovits J, Niller HH (eds) Patho-epigenetics of disease. Springer, New York, pp 379–395CrossRefGoogle Scholar
  85. Ehrlich M, Wilson GG, Kuo KC, Gehrke CW (1987) N4-methylcytosine as a minor base in bacterial DNA. J Bacteriol 169:939–943PubMedPubMedCentralCrossRefGoogle Scholar
  86. Ellison EM, Abner EL, Lovell MA (2017) Multiregional analysis of global 5-methylcytosine and 5-hydroxymethylcytosine throughout the progression of Alzheimer’s disease. J Neurochem 140:383–394PubMedPubMedCentralCrossRefGoogle Scholar
  87. Engreitz JM, Pandya-Jones A, McDonel P, Shishkin A, Sirokman K, Surka C, Kadri S, Xing J, Goren A, Lander ES, Plath K, Guttman M (2013) The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science 341:1237973PubMedPubMedCentralCrossRefGoogle Scholar
  88. Erwin JA, Marchetto MC, Gage FH (2014) Mobile DNA elements in the generation of diversity and complexity in the brain. Nat Rev Neurosci 15:497–506PubMedPubMedCentralCrossRefGoogle Scholar
  89. Erwin JA, Paquola AC, Singer T, Gallina I, Novotny M, Quayle C, Bedrosian TA, Alves FI, Butcher CR, Herdy JR, Sarkar A, Lasken RS, Muotri AR, Gage FH (2016) L1-associated genomic regions are deleted in somatic cells of the healthy human brain. Nat Neurosci 19:1583–1591PubMedPubMedCentralCrossRefGoogle Scholar
  90. Evsikov AV, Marin De Evsikova C (2016) Friend or foe: epigenetic regulation of retrotransposons in mammalian oogenesis and early development. Yale J Biol Med 89:487–497PubMedPubMedCentralGoogle Scholar
  91. Farlik M, Halbritter F, Muller F, Choudry FA, Ebert P, Klughammer J, Farrow S, Santoro A, Ciaurro V, Mathur A, Uppal R, Stunnenberg HG, Ouwehand WH, Laurenti E, Lengauer T, Frontini M, Bock C (2016) DNA methylation dynamics of human hematopoietic stem cell differentiation. Cell Stem Cell 19:808–822PubMedPubMedCentralCrossRefGoogle Scholar
  92. Farlik M, Sheffield NC, Nuzzo A, Datlinger P, Schonegger A, Klughammer J, Bock C (2015) Single-cell DNA methylome sequencing and bioinformatic inference of epigenomic cell-state dynamics. Cell Rep 10:1386–1397PubMedPubMedCentralCrossRefGoogle Scholar
  93. Farthing CR, Ficz G, Ng RK, Chan CF, Andrews S, Dean W, Hemberger M, Reik W (2008) Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes. PLoS Genet 4:e1000116PubMedPubMedCentralCrossRefGoogle Scholar
  94. Fatemi M, Hermann A, Gowher H, Jeltsch A (2002) Dnmt3a and Dnmt1 functionally cooperate during de novo methylation of DNA. Eur J Biochem 269:4981–4984PubMedCrossRefGoogle Scholar
  95. Feng S, Jacobsen SE, Reik W (2010) Epigenetic reprogramming in plant and animal development. Science 330:622–627PubMedPubMedCentralCrossRefGoogle Scholar
  96. Ficz G (2015) New insights into mechanisms that regulate DNA methylation patterning. J Exp Biol 218:14–20PubMedCrossRefGoogle Scholar
  97. Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH (2007) Recovery of learning and memory is associated with chromatin remodelling. Nature 447:178–182PubMedCrossRefGoogle Scholar
  98. Flavahan WA, Drier Y, Liau BB, Gillespie SM, Venteicher AS, Stemmer-Rachamimov AO, Suva ML, Bernstein BE (2016) Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature 529:110–114PubMedCrossRefGoogle Scholar
  99. Fouse SD, Shen Y, Pellegrini M, Cole S, Meissner A, Van Neste L, Jaenisch R, Fan G (2008) Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog, PcG complex, and histone H3 K4/K27 trimethylation. Cell Stem Cell 2:160–169PubMedPubMedCentralCrossRefGoogle Scholar
  100. Frank D, Keshet I, Shani M, Levine A, Razin A, Cedar H (1991) Demethylation of CpG islands in embryonic cells. Nature 351:239–241PubMedCrossRefGoogle Scholar
  101. Frank D, Lichtenstein M, Paroush Z, Bergman Y, Shani M, Razin A, Cedar H (1990) Demethylation of genes in animal cells. Philos Trans R Soc Lond Ser B Biol Sci 326:241–251CrossRefGoogle Scholar
  102. Fritz EL, Papavasiliou FN (2010) Cytidine deaminases: AIDing DNA demethylation? Genes Dev 24:2107–2114PubMedPubMedCentralCrossRefGoogle Scholar
  103. Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW, Molloy PL, Paul CL (1992) A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci U S A 89:1827–1831PubMedPubMedCentralCrossRefGoogle Scholar
  104. Fu A, Jacobs DI, Hoffman AE, Zheng T, Zhu Y (2015a) PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome. Carcinogenesis 36:1094–1102PubMedPubMedCentralCrossRefGoogle Scholar
  105. Fu Y, Luo GZ, Chen K, Deng X, Yu M, Han D, Hao Z, Liu J, Lu X, Dore LC, Weng X, Ji Q, Mets L, He C (2015b) N6-methyldeoxyadenosine marks active transcription start sites in Chlamydomonas. Cell 161:879–892PubMedPubMedCentralCrossRefGoogle Scholar
  106. Fujita N, Watanabe S, Ichimura T, Tsuruzoe S, Shinkai Y, Tachibana M, Chiba T, Nakao M (2003) Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J Biol Chem 278:24132–24138PubMedCrossRefGoogle Scholar
  107. Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J, Farinelli L, Miska E, Mansuy IM (2014) Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci 17:667–669PubMedPubMedCentralCrossRefGoogle Scholar
  108. Gatto S, D’Esposito M, Matarazzo MR (2012) The role of DNMT3B mutations in the pathogenesis of ICF syndrome. In: Minarovits J, Niller HH (eds) Patho-Epigenetics of disease. Springer, New York, pp 15–41CrossRefGoogle Scholar
  109. Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray JW, Leonhardt H, Jaenisch R (2003) Induction of tumors in mice by genomic hypomethylation. Science 300:489–492PubMedCrossRefGoogle Scholar
  110. Georgia S, Kanji M, Bhushan A (2013) DNMT1 represses p53 to maintain progenitor cell survival during pancreatic organogenesis. Genes Dev 27:372–377PubMedPubMedCentralCrossRefGoogle Scholar
  111. Gifford WD, Pfaff SL, Macfarlan TS (2013) Transposable elements as genetic regulatory substrates in early development. Trends Cell Biol 23:218–226PubMedPubMedCentralCrossRefGoogle Scholar
  112. Gilbert SL, Pehrson JR, Sharp PA (2000) XIST RNA associates with specific regions of the inactive X chromatin. J Biol Chem 275:36491–36494PubMedCrossRefGoogle Scholar
  113. Gilbert SL, Sharp PA (1999) Promoter-specific hypoacetylation of X-inactivated genes. Proc Natl Acad Sci U S A 96:13825–13830PubMedPubMedCentralCrossRefGoogle Scholar
  114. Ginno PA, Lim YW, Lott PL, Korf I, Chedin F (2013) GC skew at the 5′ and 3′ ends of human genes links R-loop formation to epigenetic regulation and transcription termination. Genome Res 23:1590–1600PubMedPubMedCentralCrossRefGoogle Scholar
  115. 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 45:814–825PubMedPubMedCentralCrossRefGoogle Scholar
  116. Giunta S, Funabiki H (2017) Integrity of the human centromere DNA repeats is protected by CENP-A, CENP-C, and CENP-T. Proc Natl Acad Sci U S A 114:1928–1933PubMedPubMedCentralCrossRefGoogle Scholar
  117. Gjoneska E, Pfenning AR, Mathys H, Quon G, Kundaje A, Tsai LH, Kellis M (2015) Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer’s disease. Nature 518:365–369PubMedPubMedCentralCrossRefGoogle Scholar
  118. Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL, Zhang X, Golic KG, Jacobsen SE, Bestor TH (2006) Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 311:395–398PubMedCrossRefGoogle Scholar
  119. Goodier JL (2016) Restricting retrotransposons: a review. Mob DNA 7:16PubMedPubMedCentralCrossRefGoogle Scholar
  120. Gopalakrishnan S, Sullivan BA, Trazzi S, Della Valle G, Robertson KD (2009) DNMT3B interacts with constitutive centromere protein CENP-C to modulate DNA methylation and the histone code at centromeric regions. Hum Mol Genet 18:3178–3193PubMedPubMedCentralCrossRefGoogle Scholar
  121. Gopalakrishnan S, Van Emburgh BO, Robertson KD (2008) DNA methylation in development and human disease. Mutat Res 647:30–38PubMedPubMedCentralCrossRefGoogle Scholar
  122. Gordon CA, Hartono SR, Chedin F (2013) Inactive DNMT3B splice variants modulate de novo DNA methylation. PLoS One 8:e69486PubMedPubMedCentralCrossRefGoogle Scholar
  123. Goto K, Numata M, Komura JI, Ono T, Bestor TH, Kondo H (1994) Expression of DNA methyltransferase gene in mature and immature neurons as well as proliferating cells in mice. Differentiation 56:39–44PubMedCrossRefGoogle Scholar
  124. Grammatikakis I, Abdelmohsen K, Gorospe M (2017) Posttranslational control of HuR function. Wiley Interdiscip Rev RNA 8:e1372Google Scholar
  125. Gravina S, Dong X, Yu B, Vijg J (2016) Single-cell genome-wide bisulfite sequencing uncovers extensive heterogeneity in the mouse liver methylome. Genome Biol 17:150PubMedPubMedCentralCrossRefGoogle Scholar
  126. Greer EL, Blanco MA, Gu L, Sendinc E, Liu J, Aristizabal-Corrales D, Hsu CH, Aravind L, He C, Shi Y (2015) DNA methylation on N6-adenine in C. elegans. Cell 161:868–878PubMedPubMedCentralCrossRefGoogle Scholar
  127. Grigorenko EL, Kornilov SA, Naumova OY (2016) Epigenetic regulation of cognition: a circumscribed review of the field. Dev Psychopathol 28:1285–1304PubMedCrossRefGoogle Scholar
  128. Guan Z, Giustetto M, Lomvardas S, Kim JH, Miniaci MC, Schwartz JH, Thanos D, Kandel ER (2002) Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure. Cell 111:483–493PubMedCrossRefGoogle Scholar
  129. Guibert S, Forne T, Weber M (2012) Global profiling of DNA methylation erasure in mouse primordial germ cells. Genome Res 22:633–641PubMedPubMedCentralCrossRefGoogle Scholar
  130. Guo F, Yan L, Guo H, Li L, Hu B, Zhao Y, Yong J, Hu Y, Wang X, Wei Y, Wang W, Li R, Yan J, Zhi X, Zhang Y, Jin H, Zhang W, Hou Y, Zhu P, Li J, Zhang L, Liu S, Ren Y, Zhu X, Wen L, Gao YQ, Tang F, Qiao J (2015b) The transcriptome and DNA methylome landscapes of human primordial germ cells. Cell 161:1437–1452PubMedCrossRefGoogle Scholar
  131. Guo H, Zhu P, Guo F, Li X, Wu X, Fan X, Wen L, Tang F (2015c) Profiling DNA methylome landscapes of mammalian cells with single-cell reduced-representation bisulfite sequencing. Nat Protoc 10:645–659PubMedCrossRefGoogle Scholar
  132. Guo H, Zhu P, Wu X, Li X, Wen L, Tang F (2013) Single-cell methylome landscapes of mouse embryonic stem cells and early embryos analyzed using reduced representation bisulfite sequencing. Genome Res 23:2126–2135PubMedPubMedCentralCrossRefGoogle Scholar
  133. Guo JU, Ma DK, Mo H, Ball MP, Jang MH, Bonaguidi MA, Balazer JA, Eaves HL, Xie B, Ford E, Zhang K, Ming GL, Gao Y, Song H (2011) Neuronal activity modifies the DNA methylation landscape in the adult brain. Nat Neurosci 14:1345–1351PubMedPubMedCentralCrossRefGoogle Scholar
  134. Guo X, Wang L, Li J, Ding Z, Xiao J, Yin X, He S, Shi P, Dong L, Li G, Tian C, Wang J, Cong Y, Xu Y (2015a) Structural insight into autoinhibition and histone H3-induced activation of DNMT3A. Nature 517:640–644PubMedCrossRefGoogle Scholar
  135. Gyory I, Minarovits J (2005) Epigenetic regulation of lymphoid specific gene sets. Biochem Cell Biol 83:286–295PubMedCrossRefGoogle Scholar
  136. Hackett JA, Reddington JP, Nestor CE, Dunican DS, Branco MR, Reichmann J, Reik W, Surani MA, Adams IR, Meehan RR (2012) Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline. Development 139:3623–3632PubMedPubMedCentralCrossRefGoogle Scholar
  137. Hackett JA, Surani MA (2013) DNA methylation dynamics during the mammalian life cycle. Philos Trans R Soc Lond Ser B Biol Sci 368:20110328CrossRefGoogle Scholar
  138. Hannon E, Spiers H, Viana J, Pidsley R, Burrage J, Murphy TM, Troakes C, Turecki G, O’Donovan MC, Schalkwyk LC, Bray NJ, Mill J (2016) Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci. Nat Neurosci 19:48–54PubMedCrossRefGoogle Scholar
  139. Hansen KD, Sabunciyan S, Langmead B, Nagy N, Curley R, Klein G, Klein E, Salamon D, Feinberg AP (2014) Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization. Genome Res 24:177–184PubMedPubMedCentralCrossRefGoogle Scholar
  140. Hantusch B, Kalt R, Krieger S, Puri C, Kerjaschki D (2007) Sp1/Sp3 and DNA-methylation contribute to basal transcriptional activation of human podoplanin in MG63 versus Saos-2 osteoblastic cells. BMC Mol Biol 8:20PubMedPubMedCentralCrossRefGoogle Scholar
  141. Hark AT, Schoenherr CJ, Katz DJ, Ingram RS, Levorse JM, Tilghman SM (2000) CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature 405:486–489PubMedCrossRefGoogle Scholar
  142. 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 455:826–829PubMedPubMedCentralCrossRefGoogle Scholar
  143. He XJ, Chen T, Zhu JK (2011) Regulation and function of DNA methylation in plants and animals. Cell Res 21:442–465PubMedPubMedCentralCrossRefGoogle Scholar
  144. Hermann A, Goyal R, Jeltsch A (2004) The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites. J Biol Chem 279:48350–48359PubMedCrossRefGoogle Scholar
  145. Hervouet E, Nadaradjane A, Gueguen M, Vallette FM, Cartron PF (2012) Kinetics of DNA methylation inheritance by the Dnmt1-including complexes during the cell cycle. Cell Div 7:5PubMedPubMedCentralCrossRefGoogle Scholar
  146. Hervouet E, Vallette FM, Cartron PF (2009) Dnmt3/transcription factor interactions as crucial players in targeted DNA methylation. Epigenetics 4:487–499PubMedCrossRefGoogle Scholar
  147. Hervouet E, Vallette FM, Cartron PF (2010) Dnmt1/transcription factor interactions: an alternative mechanism of DNA methylation inheritance. Genes Cancer 1:434–443PubMedPubMedCentralCrossRefGoogle Scholar
  148. Heyn H, Esteller M (2015) An adenine code for DNA: a second life for N6-methyladenine. Cell 161:710–713PubMedCrossRefGoogle Scholar
  149. Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A, Diez J, Sanchez-Mut JV, Setien F, Carmona FJ, Puca AA, Sayols S, Pujana MA, Serra-Musach J, Iglesias-Platas I, Formiga F, Fernandez AF, Fraga MF, Heath SC, Valencia A, Gut IG, Wang J, Esteller M (2012) Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci U S A 109:10522–10527PubMedPubMedCentralCrossRefGoogle Scholar
  150. Hoffmann A, Ziller M, Spengler D (2016) The future is the past: methylation QTLs in schizophrenia. Genes (Basel) 7:E104Google Scholar
  151. Holliday R, Pugh JE (1975) DNA modification mechanisms and gene activity during development. Science 187:226–232PubMedCrossRefGoogle Scholar
  152. Horvath S, Mah V, Lu AT, Woo JS, Choi OW, Jasinska AJ, Riancho JA, Tung S, Coles NS, Braun J, Vinters HV, Coles LS (2015) The cerebellum ages slowly according to the epigenetic clock. Aging (Albany NY) 7:294–306CrossRefGoogle Scholar
  153. Horvath S, Zhang Y, Langfelder P, Kahn RS, Boks MP, Van Eijk K, Van Den Berg LH, Ophoff RA (2012) Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol 13:R97PubMedPubMedCentralCrossRefGoogle Scholar
  154. Hou Y, Guo H, Cao C, Li X, Hu B, Zhu P, Wu X, Wen L, Tang F, Huang Y, Peng J (2016) Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas. Cell Res 26:304–319PubMedPubMedCentralCrossRefGoogle Scholar
  155. Howard G, Eiges R, Gaudet F, Jaenisch R, Eden A (2008) Activation and transposition of endogenous retroviral elements in hypomethylation induced tumors in mice. Oncogene 27:404–408PubMedCrossRefGoogle Scholar
  156. Howell CY, Bestor TH, Ding F, Latham KE, Mertineit C, Trasler JM, Chaillet JR (2001) Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 104:829–838PubMedCrossRefGoogle Scholar
  157. Hu Y, Huang K, An Q, Du G, Hu G, Xue J, Zhu X, Wang CY, Xue Z, Fan G (2016) Simultaneous profiling of transcriptome and DNA methylome from a single cell. Genome Biol 17:88PubMedPubMedCentralCrossRefGoogle Scholar
  158. Huang J, Fan T, Yan Q, Zhu H, Fox S, Issaq HJ, Best L, Gangi L, Munroe D, Muegge K (2004) Lsh, an epigenetic guardian of repetitive elements. Nucleic Acids Res 32:5019–5028PubMedPubMedCentralCrossRefGoogle Scholar
  159. Huang R, Ding Q, Xiang Y, Gu T, Li Y (2016) Comparative analysis of DNA methyltransferase gene family in fungi: a focus on Basidiomycota. Front Plant Sci 7:1556PubMedPubMedCentralGoogle Scholar
  160. Igaz LM, Vianna MR, Medina JH, Izquierdo I (2002) Two time periods of hippocampal mRNA synthesis are required for memory consolidation of fear-motivated learning. J Neurosci 22:6781–6789PubMedGoogle Scholar
  161. 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 7:997–1007PubMedCrossRefGoogle Scholar
  162. Ishikawa K, Fukuda E, Kobayashi I (2010) Conflicts targeting epigenetic systems and their resolution by cell death: novel concepts for methyl-specific and other restriction systems. DNA Res 17:325–342PubMedPubMedCentralCrossRefGoogle Scholar
  163. Iyer LM, Abhiman S, Aravind L (2011) Natural history of eukaryotic DNA methylation systems. Prog Mol Biol Transl Sci 101:25–104PubMedCrossRefGoogle Scholar
  164. Jaffe AE, Gao Y, Deep-Soboslay A, Tao R, Hyde TM, Weinberger DR, Kleinman JE (2016) Mapping DNA methylation across development, genotype and schizophrenia in the human frontal cortex. Nat Neurosci 19:40–47PubMedCrossRefGoogle Scholar
  165. Jeltsch A (2006) On the enzymatic properties of Dnmt1: specificity, processivity, mechanism of linear diffusion and allosteric regulation of the enzyme. Epigenetics 1:63–66PubMedCrossRefGoogle Scholar
  166. Jeltsch A (2013) Oxygen, epigenetic signaling, and the evolution of early life. Trends BiochemSci 38:172–176CrossRefGoogle Scholar
  167. Jeltsch A, Jurkowska RZ (2016) Allosteric control of mammalian DNA methyltransferases – a new regulatory paradigm. Nucleic Acids Res 44:8556–8575PubMedPubMedCentralCrossRefGoogle Scholar
  168. Jeon J, Choi J, Lee GW, Park SY, Huh A, Dean RA, Lee YH (2015) Genome-wide profiling of DNA methylation provides insights into epigenetic regulation of fungal development in a plant pathogenic fungus, Magnaporthe oryzae. Sci Rep 5:8567PubMedPubMedCentralCrossRefGoogle Scholar
  169. Jeong S, Liang G, Sharma S, Lin JC, Choi SH, Han H, Yoo CB, Egger G, Yang AS, Jones PA (2009) Selective anchoring of DNA methyltransferases 3A and 3B to nucleosomes containing methylated DNA. MolCell Biol 29:5366–5376Google Scholar
  170. Jessberger S, Nakashima K, Clemenson GD Jr, Mejia E, Mathews E, Ure K, Ogawa S, Sinton CM, Gage FH, Hsieh J (2007) Epigenetic modulation of seizure-induced neurogenesis and cognitive decline. J Neurosci 27:5967–5975PubMedCrossRefGoogle Scholar
  171. Ji D, Lin K, Song J, Wang Y (2014) Effects of Tet-induced oxidation products of 5-methylcytosine on Dnmt1- and DNMT3a-mediated cytosine methylation. Mol BioSyst 10:1749–1752PubMedPubMedCentralCrossRefGoogle Scholar
  172. Ji H, Ehrlich LI, Seita J, Murakami P, Doi A, Lindau P, Lee H, Aryee MJ, Irizarry RA, Kim K, Rossi DJ, Inlay MA, Serwold T, Karsunky H, Ho L, Daley GQ, Weissman IL, Feinberg AP (2010) Comprehensive methylome map of lineage commitment from haematopoietic progenitors. Nature 467:338–342PubMedPubMedCentralCrossRefGoogle Scholar
  173. 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 449:248–251PubMedPubMedCentralCrossRefGoogle Scholar
  174. Jiang N, Wang L, Chen J, Wang L, Leach L, Luo Z (2014) Conserved and divergent patterns of DNA methylation in higher vertebrates. Genome Biol Evol 6:2998–3014PubMedPubMedCentralCrossRefGoogle Scholar
  175. Jin B, Li Y, Robertson KD (2011) DNA methylation: superior or subordinate in the epigenetic hierarchy? Genes Cancer 2:607–617PubMedPubMedCentralCrossRefGoogle Scholar
  176. Jin B, Robertson KD (2013) DNA methyltransferases, DNA damage repair, and cancer. Adv Exp Med Biol 754:3–29PubMedPubMedCentralCrossRefGoogle Scholar
  177. Jinawath A, Miyake S, Yanagisawa Y, Akiyama Y, Yuasa Y (2005) Transcriptional regulation of the human DNA methyltransferase 3A and 3B genes by Sp3 and Sp1 zinc finger proteins. Biochem J 385:557–564PubMedPubMedCentralCrossRefGoogle Scholar
  178. Joh RI, Palmieri CM, Hill IT, Motamedi M (2014) Regulation of histone methylation by noncoding RNAs. Biochim Biophys Acta 1839:1385–1394PubMedPubMedCentralCrossRefGoogle Scholar
  179. Jones PA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13:484–492PubMedCrossRefGoogle Scholar
  180. Jones PA, Liang G (2009) Rethinking how DNA methylation patterns are maintained. NatRevGenet 10:805–811Google Scholar
  181. Jones PA, Takai D (2001) The role of DNA methylation in mammalian epigenetics. Science 293:1068–1070PubMedCrossRefGoogle Scholar
  182. 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 19:187–191PubMedCrossRefGoogle Scholar
  183. Juraeva D, Haenisch B, Zapatka M, Frank J, Investigators G, Group, P.-G.S.W, Witt SH, Muhleisen TW, Treutlein J, Strohmaier J, Meier S, Degenhardt F, Giegling I, Ripke S, Leber M, Lange C, Schulze TG, Mossner R, Nenadic I, Sauer H, Rujescu D, Maier W, Borglum A, Ophoff R, Cichon S, Nothen MM, Rietschel M, Mattheisen M, Brors B (2014) Integrated pathway-based approach identifies association between genomic regions at CTCF and CACNB2 and schizophrenia. PLoS Genet 10:e1004345PubMedPubMedCentralCrossRefGoogle Scholar
  184. Jurkowska RZ, Jeltsch A (2016) Enzymology of mammalian DNA methyltransferases. Adv Exp Med Biol 945:87–122PubMedCrossRefGoogle Scholar
  185. Jurkowski TP, Jeltsch A (2011) On the evolutionary origin of eukaryotic DNA methyltransferases and Dnmt2. PLoSOne 6:e28104CrossRefGoogle Scholar
  186. Kaas GA, Zhong C, Eason DE, Ross DL, Vachhani RV, Ming GL, King JR, Song H, Sweatt JD (2013) TET1 controls CNS 5-methylcytosine hydroxylation, active DNA demethylation, gene transcription, and memory formation. Neuron 79:1086–1093PubMedCrossRefGoogle Scholar
  187. Kaneda M, Sado T, Hata K, Okano M, Tsujimoto N, Li E, Sasaki H (2004) Role of de novo DNA methyltransferases in initiation of genomic imprinting and X-chromosome inactivation. Cold Spring Harb Symp Quant Biol 69:125–129PubMedCrossRefGoogle Scholar
  188. Kang J, Kalantry S, Rao A (2013) PGC7, H3K9me2 and Tet3: regulators of DNA methylation in zygotes. Cell Res 23:6–9PubMedCrossRefGoogle Scholar
  189. Keil KP, Vezina CM (2015) DNA methylation as a dynamic regulator of development and disease processes: spotlight on the prostate. Epigenomics 7:413–425PubMedPubMedCentralCrossRefGoogle Scholar
  190. Kelley RI (1973) Isolation of a histone IIb1-IIb2 complex. Biochem Biophys Res Commun 54:1588–1594PubMedCrossRefGoogle Scholar
  191. Kelsey G, Feil R (2013) New insights into establishment and maintenance of DNA methylation imprints in mammals. Philos Trans R Soc Lond Ser B Biol Sci 368:20110336CrossRefGoogle Scholar
  192. Khare T, Pai S, Koncevicius K, Pal M, Kriukiene E, Liutkeviciute Z, Irimia M, Jia P, Ptak C, Xia M, Tice R, Tochigi M, Morera S, Nazarians A, Belsham D, Wong AH, Blencowe BJ, Wang SC, Kapranov P, Kustra R, Labrie V, Klimasauskas S, Petronis A (2012) 5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary. Nat Struct Mol Biol 19:1037–1043PubMedPubMedCentralCrossRefGoogle Scholar
  193. Kim-Ha J, Kim YJ (2016) Age-related epigenetic regulation in the brain and its role in neuronal diseases. BMB Rep 49:671–680PubMedPubMedCentralCrossRefGoogle Scholar
  194. Kim S, Kaang BK (2017) Epigenetic regulation and chromatin remodeling in learning and memory. Exp Mol Med 49:e281PubMedPubMedCentralCrossRefGoogle Scholar
  195. Kishikawa S, Murata T, Kimura H, Shiota K, Yokoyama KK (2002) Regulation of transcription of the Dnmt1 gene by Sp1 and Sp3 zinc finger proteins. Eur J Biochem 269:2961–2970PubMedCrossRefGoogle Scholar
  196. Klausz B, Haller J, Tulogdi A, Zelena D (2012) Genetic and epigenetic determinants of aggression. In: Minarovits J, Niller HH (eds) Patho-Epigenetics of Disease. Springer, New York, pp 227–280CrossRefGoogle Scholar
  197. Klein HU, De Jager PL (2016) Uncovering the role of the Methylome in dementia and neurodegeneration. Trends Mol Med 22:687–700PubMedCrossRefGoogle Scholar
  198. Kornberg RD (1974) Chromatin structure: a repeating unit of histones and DNA. Science 184:868–871PubMedCrossRefGoogle Scholar
  199. Koziol MJ, Bradshaw CR, Allen GE, Costa AS, Frezza C, Gurdon JB (2016) Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nat Struct Mol Biol 23:24–30PubMedCrossRefGoogle Scholar
  200. Kramer B, Kramer W, Fritz HJ (1984) Different base/base mismatches are corrected with different efficiencies by the methyl-directed DNA mismatch-repair system of E. coli. Cell 38:879–887PubMedCrossRefGoogle Scholar
  201. Kremenskoy M, Kremenska Y, Ohgane J, Hattori N, Tanaka S, Hashizume K, Shiota K (2003) Genome-wide analysis of DNA methylation status of CpG islands in embryoid bodies, teratomas, and fetuses. Biochem Biophys Res Commun 311:884–890PubMedCrossRefGoogle Scholar
  202. Kriaucionis S, Heintz N (2009) The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324:929–930PubMedPubMedCentralCrossRefGoogle Scholar
  203. Kunnath L, Locker J (1982) Variable methylation of the ribosomal RNA genes of the rat. Nucleic Acids Res 10:3877–3892PubMedPubMedCentralCrossRefGoogle Scholar
  204. Kurukuti S, Tiwari VK, Tavoosidana G, Pugacheva E, Murrell A, Zhao Z, Lobanenkov V, Reik W, Ohlsson R (2006) CTCF binding at the H19 imprinting control region mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to Igf2. Proc Natl Acad Sci U S A 103:10684–10689PubMedPubMedCentralCrossRefGoogle Scholar
  205. Labrie V, Pai S, Petronis A (2012) Epigenetics of major psychosis: progress, problems and perspectives. Trends Genet 28:427–435PubMedPubMedCentralCrossRefGoogle Scholar
  206. Lahiri DK, Maloney B, Zawia NH (2009) The LEARn model: an epigenetic explanation for idiopathic neurobiological diseases. Mol Psychiatry 14:992–1003PubMedCrossRefPubMedCentralGoogle Scholar
  207. Li E, Beard C, Jaenisch R (1993) Role for DNA methylation in genomic imprinting. Nature 366:362–365PubMedCrossRefGoogle Scholar
  208. Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–926PubMedCrossRefGoogle Scholar
  209. Li E, Zhang Y (2014) DNA methylation in mammals. Cold Spring Harb Perspect Biol 6:a019133PubMedPubMedCentralCrossRefGoogle Scholar
  210. Li N, Shen Q, Hua J (2016) Epigenetic Remodeling in Male Germline Development. Stem Cells Int 2016:3152173PubMedPubMedCentralGoogle Scholar
  211. Li X, Wei W, Zhao QY, Widagdo J, Baker-Andresen D, Flavell CR, D’alessio A, Zhang Y, Bredy TW (2014) Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation. Proc Natl Acad Sci U S A 111:7120–7125PubMedPubMedCentralCrossRefGoogle Scholar
  212. 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 22:480–491PubMedPubMedCentralCrossRefGoogle Scholar
  213. Lin RK, Wang YC (2014) Dysregulated transcriptional and post-translational control of DNA methyltransferases in cancer. Cell Biosci 4:46PubMedPubMedCentralCrossRefGoogle Scholar
  214. Lin RK, Wu CY, Chang JW, Juan LJ, Hsu HS, Chen CY, Lu YY, Tang YA, Yang YC, Yang PC, Wang YC (2010) Dysregulation of p53/Sp1 control leads to DNA methyltransferase-1 overexpression in lung cancer. Cancer Res 70:5807–5817PubMedCrossRefGoogle Scholar
  215. Lin S, Gregory RI (2015) MicroRNA biogenesis pathways in cancer. Nat Rev Cancer 15:321–333PubMedPubMedCentralCrossRefGoogle Scholar
  216. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, Lucero J, Huang Y, Dwork AJ, Schultz MD, Yu M, Tonti-Filippini J, Heyn H, Hu S, Wu JC, Rao A, Esteller M, He C, Haghighi FG, Sejnowski TJ, Behrens MM, Ecker JR (2013) Global epigenomic reconfiguration during mammalian brain development. Science 341:1237905PubMedPubMedCentralCrossRefGoogle Scholar
  217. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462:315–322PubMedPubMedCentralCrossRefGoogle Scholar
  218. Liu J, Zhu Y, Luo GZ, Wang X, Yue Y, Wang X, Zong X, Chen K, Yin H, Fu Y, Han D, Wang Y, Chen D, He C (2016) Abundant DNA 6mA methylation during early embryogenesis of zebrafish and pig. Nat Commun 7:13052PubMedPubMedCentralCrossRefGoogle Scholar
  219. Liu Y, Li X (2012) Darwin’s pangenesis and molecular medicine. Trends Mol Med 18:506–508PubMedCrossRefGoogle Scholar
  220. Lopez De Silanes I, Gorospe M, Taniguchi H, Abdelmohsen K, Srikantan S, Alaminos M, Berdasco M, Urdinguio RG, Fraga MF, Jacinto FV, Esteller M (2009) The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA. Nucleic Acids Res 37:2658–2671PubMedPubMedCentralCrossRefGoogle Scholar
  221. Lubin FD, Roth TL, Sweatt JD (2008) Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J Neurosci 28:10576–10586PubMedPubMedCentralCrossRefGoogle Scholar
  222. Luo C, Lancaster MA, Castanon R, Nery JR, Knoblich JA, Ecker JR (2016) Cerebral organoids recapitulate epigenomic signatures of the human fetal brain. Cell Rep 17:3369–3384PubMedPubMedCentralCrossRefGoogle Scholar
  223. Macfarlan TS, Gifford WD, Driscoll S, Lettieri K, Rowe HM, Bonanomi D, Firth A, Singer O, Trono D, Pfaff SL (2012) Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature 487:57–63PubMedPubMedCentralCrossRefGoogle Scholar
  224. Maegawa S, Hinkal G, Kim HS, Shen L, Zhang L, Zhang J, Zhang N, Liang S, Donehower LA, Issa JP (2010) Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res 20:332–340PubMedPubMedCentralCrossRefGoogle Scholar
  225. Makarova KS, Wolf YI, Koonin EV (2013) Comparative genomics of defense systems in archaea and bacteria. Nucleic Acids Res 41:4360–4377PubMedPubMedCentralCrossRefGoogle Scholar
  226. Maloney B, Lahiri DK (2016) Epigenetics of dementia: understanding the disease as a transformation rather than a state. Lancet Neurol 15:760–774PubMedCrossRefGoogle Scholar
  227. Margot JB, Aguirre-Arteta AM, Di Giacco BV, Pradhan S, Roberts RJ, Cardoso MC, Leonhardt H (2000) Structure and function of the mouse DNA methyltransferase gene: Dnmt1 shows a tripartite structure. J Mol Biol 297:293–300PubMedCrossRefGoogle Scholar
  228. Marina RJ, Sturgill D, Bailly MA, Thenoz M, Varma G, Prigge MF, Nanan KK, Shukla S, Haque N, Oberdoerffer S (2016) TET-catalyzed oxidation of intragenic 5-methylcytosine regulates CTCF-dependent alternative splicing. EMBO J 35:335–355PubMedCrossRefGoogle Scholar
  229. Marino-Ramirez L, Kann MG, Shoemaker BA, Landsman D (2005) Histone structure and nucleosome stability. Expert Rev Proteomics 2:719–729PubMedPubMedCentralCrossRefGoogle Scholar
  230. Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun YE (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302:890–893PubMedCrossRefGoogle Scholar
  231. Maunakea AK, Chepelev I, Cui K, Zhao K (2013) Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition. Cell Res 23:1256–1269PubMedPubMedCentralCrossRefGoogle Scholar
  232. McCabe MT, Davis JN, Day ML (2005) Regulation of DNA methyltransferase 1 by the pRb/E2F1 pathway. Cancer Res 65:3624–3632PubMedCrossRefGoogle Scholar
  233. Mendizabal I, Shi L, Keller TE, Konopka G, Preuss TM, Hsieh TF, Hu E, Zhang Z, Su B, Yi SV (2016) Comparative methylome analyses identify epigenetic regulatory loci of human brain evolution. Mol Biol Evol 33:2947–2959PubMedPubMedCentralCrossRefGoogle Scholar
  234. Meng H, Cao Y, Qin J, Song X, Zhang Q, Shi Y, Cao L (2015) DNA methylation, its mediators and genome integrity. Int J Biol Sci 11:604–617PubMedPubMedCentralCrossRefGoogle Scholar
  235. Messerschmidt DM, Knowles BB, Solter D (2014) DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev 28:812–828PubMedPubMedCentralCrossRefGoogle Scholar
  236. Meyer KD, Jaffrey SR (2016) Expanding the diversity of DNA base modifications with N(6)-methyldeoxyadenosine. Genome Biol 17:5PubMedPubMedCentralCrossRefGoogle Scholar
  237. Miller CA, Gavin CF, White JA, Parrish RR, Honasoge A, Yancey CR, Rivera IM, Rubio MD, Rumbaugh G, Sweatt JD (2010) Cortical DNA methylation maintains remote memory. Nat Neurosci 13:664–666PubMedPubMedCentralCrossRefGoogle Scholar
  238. Miller CA, Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53:857–869PubMedCrossRefGoogle Scholar
  239. Minarovits J, Banati F, Szenthe K, Niller HH (2016) Epigenetic regulation. Adv Exp Med Biol 879:1–25PubMedCrossRefGoogle Scholar
  240. Minarovits J, Niller HH (2012) Patho-epigenetics of disease. Springer, New YorkCrossRefGoogle Scholar
  241. Minarovits J, Niller HH (2016) Patho-epigenetics of infectious disease. Springer, New YorkCrossRefGoogle Scholar
  242. Minarovits J, Niller HH (2017) Current Trends and alternative scenarios in EBV research. Methods Mol Biol 1532:1–32PubMedCrossRefGoogle Scholar
  243. Miousse IR, Koturbash I (2015) The fine LINE: methylation drawing the cancer landscape. Biomed Res Int 2015:131547PubMedPubMedCentralCrossRefGoogle Scholar
  244. Moll UM, Petrenko O (2003) The MDM2-p53 interaction. Mol Cancer Res 1:1001–1008PubMedGoogle Scholar
  245. Monti B, Polazzi E, Contestabile A (2009) Biochemical, molecular and epigenetic mechanisms of valproic acid neuroprotection. Curr Mol Pharmacol 2:95–109PubMedCrossRefGoogle Scholar
  246. Moore LD, Le T, Fan G (2013) DNA methylation and its basic function. Neuropsychopharmacology 38:23–38PubMedCrossRefGoogle Scholar
  247. Morgan HD, Santos F, Green K, Dean W, Reik W (2005) Epigenetic reprogramming in mammals. Hum Mol Genet 14(1):R47–R58PubMedCrossRefGoogle Scholar
  248. Moroz LL, Kohn AB (2013) Single-neuron transcriptome and methylome sequencing for epigenomic analysis of aging. Methods Mol Biol 1048:323–352PubMedPubMedCentralCrossRefGoogle Scholar
  249. Munoz-Lopez M, Garcia-Perez JL (2010) DNA transposons: nature and applications in genomics. Curr Genomics 11:115–128PubMedPubMedCentralCrossRefGoogle Scholar
  250. Muotri AR, Marchetto MC, Coufal NG, Oefner R, Yeo G, Nakashima K, Gage FH (2010) L1 retrotransposition in neurons is modulated by MeCP2. Nature 468:443–446PubMedPubMedCentralCrossRefGoogle Scholar
  251. Nakamura T, Liu YJ, Nakashima H, Umehara H, Inoue K, Matoba S, Tachibana M, Ogura A, Shinkai Y, Nakano T (2012) PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos. Nature 486:415–419PubMedGoogle Scholar
  252. 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 393:386–389PubMedCrossRefGoogle Scholar
  253. Nativio R, Wendt KS, Ito Y, Huddleston JE, Uribe-Lewis S, Woodfine K, Krueger C, Reik W, Peters JM, Murrell A (2009) Cohesin is required for higher-order chromatin conformation at the imprinted IGF2-H19 locus. PLoS Genet 5:e1000739PubMedPubMedCentralCrossRefGoogle Scholar
  254. Niesen MI, Osborne AR, Yang H, Rastogi S, Chellappan S, Cheng JQ, Boss JM, Blanck G (2005) Activation of a methylated promoter mediated by a sequence-specific DNA-binding protein, RFX. J Biol Chem 280:38914–38922PubMedCrossRefGoogle Scholar
  255. Nikolova YS, Hariri AR (2015) Can we observe epigenetic effects on human brain function? Trends Cogn Sci 19:366–373PubMedPubMedCentralCrossRefGoogle Scholar
  256. Ogden GB, Pratt MJ, Schaechter M (1988) The replicative origin of the E. coli chromosome binds to cell membranes only when hemimethylated. Cell 54:127–135PubMedCrossRefGoogle Scholar
  257. Oh G, Ebrahimi S, Wang SC, Cortese R, Kaminsky ZA, Gottesman I, Burke JR, Plassman BL, Petronis A (2016) Epigenetic assimilation in the aging human brain. Genome Biol 17:76PubMedPubMedCentralCrossRefGoogle Scholar
  258. Oh G, Wang SC, Pal M, Chen ZF, Khare T, Tochigi M, Ng C, Yang YA, Kwan A, Kaminsky ZA, Mill J, Gunasinghe C, Tackett JL, Gottesman I, Willemsen G, De Geus EJ, Vink JM, Slagboom PE, Wray NR, Heath AC, Montgomery GW, Turecki G, Martin NG, Boomsma DI, McGuffin P, Kustra R, Petronis A (2015) DNA modification study of major depressive disorder: beyond locus-by-locus comparisons. Biol Psychiatry 77:246–255PubMedCrossRefGoogle Scholar
  259. Okada T, Ohzeki J, Nakano M, Yoda K, Brinkley WR, Larionov V, Masumoto H (2007) CENP-B controls centromere formation depending on the chromatin context. Cell 131:1287–1300PubMedCrossRefGoogle Scholar
  260. Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257PubMedCrossRefGoogle Scholar
  261. Oliveira AM, Hemstedt TJ, Bading H (2012) Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities. Nat Neurosci 15:1111–1113PubMedCrossRefGoogle Scholar
  262. Ostler KR, Davis EM, Payne SL, Gosalia BB, Exposito-Cespedes J, Le Beau MM, Godley LA (2007) Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins. Oncogene 26:5553–5563PubMedPubMedCentralCrossRefGoogle Scholar
  263. Pandya-Jones A, Plath K (2016) The "lnc" between 3D chromatin structure and X chromosome inactivation. Semin Cell Dev Biol 56:35–47PubMedPubMedCentralCrossRefGoogle Scholar
  264. Pearson CE, Nichol Edamura K, Cleary JD (2005) Repeat instability: mechanisms of dynamic mutations. Nat Rev Genet 6:729–742PubMedCrossRefGoogle Scholar
  265. Peaston AE, Evsikov AV, Graber JH, De Vries WN, Holbrook AE, Solter D, Knowles BB (2004) Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Dev Cell 7:597–606PubMedCrossRefGoogle Scholar
  266. Peterson EJ, Bogler O, Taylor SM (2003) p53-mediated repression of DNA methyltransferase 1 expression by specific DNA binding. Cancer Res 63:6579–6582PubMedGoogle Scholar
  267. Petrussa L, Van De Velde H, De Rycke M (2014) Dynamic regulation of DNA methyltransferases in human oocytes and preimplantation embryos after assisted reproductive technologies. Mol Hum Reprod 20:861–874PubMedCrossRefGoogle Scholar
  268. Pfaffeneder T, Spada F, Wagner M, Brandmayr C, Laube SK, Eisen D, Truss M, Steinbacher J, Hackner B, Kotljarova O, Schuermann D, Michalakis S, Kosmatchev O, Schiesser S, Steigenberger B, Raddaoui N, Kashiwazaki G, Muller U, Spruijt CG, Vermeulen M, Leonhardt H, Schar P, Muller M, Carell T (2014) Tet oxidizes thymine to 5-hydroxymethyluracil in mouse embryonic stem cell DNA. Nat Chem Biol 10:574–581PubMedCrossRefGoogle Scholar
  269. Ponts N, Fu L, Harris EY, Zhang J, Chung DW, Cervantes MC, Prudhomme J, Atanasova-Penichon V, Zehraoui E, Bunnik EM, Rodrigues EM, Lonardi S, Hicks GR, Wang Y, Le Roch KG (2013) Genome-wide mapping of DNA methylation in the human malaria parasite plasmodium falciparum. Cell Host Microbe 14:696–706PubMedPubMedCentralCrossRefGoogle Scholar
  270. Posfai J, Bhagwat AS, Posfai G, Roberts RJ (1989) Predictive motifs derived from cytosine methyltransferases. Nucleic Acids Res 17:2421–2435PubMedPubMedCentralCrossRefGoogle Scholar
  271. 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 274:33002–33010PubMedCrossRefGoogle Scholar
  272. Putiri EL, Robertson KD (2011) Epigenetic mechanisms and genome stability. Clin Epigenetics 2:299–314PubMedCrossRefGoogle Scholar
  273. Qin W, Leonhardt H, Pichler G (2011) Regulation of DNA methyltransferase 1 by interactions and modifications. Nucleus 2:392–402PubMedCrossRefGoogle Scholar
  274. Quenneville S, Turelli P, Bojkowska K, Raclot C, Offner S, Kapopoulou A, Trono D (2012) The KRAB-ZFP/KAP1 system contributes to the early embryonic establishment of site-specific DNA methylation patterns maintained during development. Cell Rep 2:766–773PubMedPubMedCentralCrossRefGoogle Scholar
  275. Rajasethupathy P, Antonov I, Sheridan R, Frey S, Sander C, Tuschl T, Kandel ER (2012) A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell 149:693–707PubMedPubMedCentralCrossRefGoogle Scholar
  276. Rasmussen KD, Helin K (2016) Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev 30:733–750PubMedPubMedCentralCrossRefGoogle Scholar
  277. Ratnam S, Mertineit C, Ding F, Howell CY, Clarke HJ, Bestor TH, Chaillet JR, Trasler JM (2002) Dynamics of Dnmt1 methyltransferase expression and intracellular localization during oogenesis and preimplantation development. Dev Biol 245:304–314PubMedCrossRefGoogle Scholar
  278. Rebhandl S, Huemer M, Greil R, Geisberger R (2015) AID/APOBEC deaminases and cancer. Oncoscience 2:320–333PubMedPubMedCentralCrossRefGoogle Scholar
  279. Reddy K, Tam M, Bowater RP, Barber M, Tomlinson M, Nichol Edamura K, Wang YH, Pearson CE (2011) Determinants of R-loop formation at convergent bidirectionally transcribed trinucleotide repeats. Nucleic Acids Res 39:1749–1762PubMedCrossRefGoogle Scholar
  280. Reik W (2007) Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447:425–432PubMedCrossRefGoogle Scholar
  281. Reik W, Walter J (1998) Imprinting mechanisms in mammals. Curr Opin Genet Dev 8:154–164PubMedCrossRefGoogle Scholar
  282. Renfree MB, Suzuki S, Kaneko-Ishino T (2013) The origin and evolution of genomic imprinting and viviparity in mammals. Philos Trans R Soc Lond Ser B Biol Sci 368:20120151CrossRefGoogle Scholar
  283. Riggs AD (1975) X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet 14:9–25PubMedCrossRefGoogle Scholar
  284. Robertson KD (2001) DNA methylation, methyltransferases, and cancer. Oncogene 20:3139–3155PubMedCrossRefGoogle Scholar
  285. Rodriguez-Osorio N, Wang H, Rupinski J, Bridges SM, Memili E (2010) Comparative functional genomics of mammalian DNA methyltransferases. Reprod Biomed Online 20:243–255PubMedCrossRefGoogle Scholar
  286. Rogers SD, Rogers ME, Saunders G, Holt G (1986) Isolation of mutants sensitive to 2-aminopurine and alkylating agents and evidence for the role of DNA methylation in Penicillium chrysogenum. Curr Genet 10:557–560PubMedCrossRefGoogle Scholar
  287. Rudenko A, Dawlaty MM, Seo J, Cheng AW, Meng J, Le T, Faull KF, Jaenisch R, Tsai LH (2013) Tet1 is critical for neuronal activity-regulated gene expression and memory extinction. Neuron 79:1109–1122PubMedPubMedCentralCrossRefGoogle Scholar
  288. Saadeh H, Schulz R (2014) Protection of CpG islands against de novo DNA methylation during oogenesis is associated with the recognition site of E2f1 and E2f2. Epigenetics Chromatin 7:26PubMedPubMedCentralCrossRefGoogle Scholar
  289. Saitou M, Yamaji M (2012) Primordial germ cells in mice. Cold Spring Harb Perspect Biol 4:a008375Google Scholar
  290. Sakamoto Y, Watanabe S, Ichimura T, Kawasuji M, Koseki H, Baba H, Nakao M (2007) Overlapping roles of the methylated DNA-binding protein MBD1 and polycomb group proteins in transcriptional repression of HOXA genes and heterochromatin foci formation. J Biol Chem 282:16391–16400PubMedCrossRefGoogle Scholar
  291. Sanchez-Mut JV, Heyn H, Vidal E, Delgado-Morales R, Moran S, Sayols S, Sandoval J, Ferrer I, Esteller M, Graff J (2017) Whole genome grey and white matter DNA methylation profiles in dorsolateral prefrontal cortex. Synapse 71:e21959.
  292. Sanchez-Mut JV, Heyn H, Vidal E, Moran S, Sayols S, Delgado-Morales R, Schultz MD, Ansoleaga B, Garcia-Esparcia P, Pons-Espinal M, De Lagran MM, Dopazo J, Rabano A, Avila J, Dierssen M, Lott I, Ferrer I, Ecker JR, Esteller M (2016) Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns. Transl Psychiatry 6:e718PubMedPubMedCentralCrossRefGoogle Scholar
  293. Sasaki H, Ishihara K, Kato R (2000) Mechanisms of Igf2/H19 imprinting: DNA methylation, chromatin and long-distance gene regulation. J Biochem 127:711–715PubMedCrossRefGoogle Scholar
  294. Sawaya S, Bagshaw A, Buschiazzo E, Kumar P, Chowdhury S, Black MA, Gemmell N (2013) Microsatellite tandem repeats are abundant in human promoters and are associated with regulatory elements. PLoS One 8:e54710PubMedPubMedCentralCrossRefGoogle Scholar
  295. Sawaya S, Boocock J, Black MA, Gemmell NJ (2015) Exploring possible DNA structures in real-time polymerase kinetics using Pacific biosciences sequencer data. BMC Bioinformatics 16:21PubMedPubMedCentralCrossRefGoogle Scholar
  296. Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511:421–427PubMedCentralCrossRefGoogle Scholar
  297. Schneider E, Dittrich M, Bock J, Nanda I, Muller T, Seidmann L, Tralau T, Galetzka D, El Hajj N, Haaf T (2016) CpG sites with continuously increasing or decreasing methylation from early to late human fetal brain development. Gene 592:110–118PubMedCrossRefGoogle Scholar
  298. Schneider K, Fuchs C, Dobay A, Rottach A, Qin W, Wolf P, Alvarez-Castro JM, Nalaskowski MM, Kremmer E, Schmid V, Leonhardt H, Schermelleh L (2013) Dissection of cell cycle-dependent dynamics of Dnmt1 by FRAP and diffusion-coupled modeling. Nucleic Acids Res 41:4860–4876PubMedPubMedCentralCrossRefGoogle Scholar
  299. Schrader A, Gross T, Thalhammer V, Langst G (2015) Characterization of Dnmt1 binding and DNA methylation on nucleosomes and nucleosomal arrays. PLoS One 10:e0140076PubMedPubMedCentralCrossRefGoogle Scholar
  300. Schultz MD, He Y, Whitaker JW, Hariharan M, Mukamel EA, Leung D, Rajagopal N, Nery JR, Urich MA, Chen H, Lin S, Lin Y, Jung I, Schmitt AD, Selvaraj S, Ren B, Sejnowski TJ, Wang W, Ecker JR (2015) Human body epigenome maps reveal noncanonical DNA methylation variation. Nature 523:212–216PubMedPubMedCentralCrossRefGoogle Scholar
  301. Scott A, Song J, Ewing R, Wang Z (2014) Regulation of protein stability of DNA methyltransferase 1 by post-translational modifications. Acta Biochim Biophys Sin Shanghai 46:199–203PubMedPubMedCentralCrossRefGoogle Scholar
  302. Sdek P, Ying H, Chang DL, Qiu W, Zheng H, Touitou R, Allday MJ, Xiao ZX (2005) MDM2 promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma protein. Mol Cell 20:699–708PubMedCrossRefGoogle Scholar
  303. Seisenberger S, Peat JR, Hore TA, Santos F, Dean W, Reik W (2013a) Reprogramming DNA methylation in the mammalian life cycle: building and breaking epigenetic barriers. Philos Trans R Soc Lond Ser B Biol Sci 368:20110330CrossRefGoogle Scholar
  304. Seisenberger S, Peat JR, Reik W (2013b) Conceptual links between DNA methylation reprogramming in the early embryo and primordial germ cells. Curr Opin Cell Biol 25:281–288PubMedCrossRefGoogle Scholar
  305. Serandour AA, Avner S, Percevault F, Demay F, Bizot M, Lucchetti-Miganeh C, Barloy-Hubler F, Brown M, Lupien M, Metivier R, Salbert G, Eeckhoute J (2011) Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers. Genome Res 21:555–565PubMedPubMedCentralCrossRefGoogle Scholar
  306. Shabbir MA, Hao H, Shabbir MZ, Wu Q, Sattar A, Yuan Z (2016) Bacteria vs. bacteriophages: parallel evolution of immune arsenals. Front Microbiol 7:1292PubMedPubMedCentralCrossRefGoogle Scholar
  307. Sharp AJ, Stathaki E, Migliavacca E, Brahmachary M, Montgomery SB, Dupre Y, Antonarakis SE (2011) DNA methylation profiles of human active and inactive X chromosomes. Genome Res 21:1592–1600PubMedPubMedCentralCrossRefGoogle Scholar
  308. Shukla S, Kavak E, Gregory M, Imashimizu M, Shutinoski B, Kashlev M, Oberdoerffer P, Sandberg R, Oberdoerffer S (2011) CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Nature 479:74–79PubMedCrossRefGoogle Scholar
  309. Shukla S, Oberdoerffer S (2012) Co-transcriptional regulation of alternative pre-mRNA splicing. Biochim Biophys Acta 1819:673–683PubMedPubMedCentralCrossRefGoogle Scholar
  310. Shukla V, Coumoul X, Lahusen T, Wang RH, Xu X, Vassilopoulos A, Xiao C, Lee MH, Man YG, Ouchi M, Ouchi T, Deng CX (2010) BRCA1 affects global DNA methylation through regulation of DNMT1. Cell Res 20:1201–1215PubMedCrossRefGoogle Scholar
  311. Sigurdsson MI, Smith AV, Bjornsson HT, Jonsson JJ (2009) HapMap methylation-associated SNPs, markers of germline DNA methylation, positively correlate with regional levels of human meiotic recombination. Genome Res 19:581–589PubMedPubMedCentralCrossRefGoogle Scholar
  312. Smallwood SA, Lee HJ, Angermueller C, Krueger F, Saadeh H, Peat J, Andrews SR, Stegle O, Reik W, Kelsey G (2014) Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Nat Methods 11:817–820PubMedPubMedCentralCrossRefGoogle Scholar
  313. Smeets D, Markaki Y, Schmid VJ, Kraus F, Tattermusch A, Cerase A, Sterr M, Fiedler S, Demmerle J, Popken J, Leonhardt H, Brockdorff N, Cremer T, Schermelleh L, Cremer M (2014) Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci. Epigenetics Chromatin 7:8PubMedPubMedCentralCrossRefGoogle Scholar
  314. Smith AK, Kilaru V, Klengel T, Mercer KB, Bradley B, Conneely KN, Ressler KJ, Binder EB (2015) DNA extracted from saliva for methylation studies of psychiatric traits: evidence tissue specificity and relatedness to brain. Am J Med Genet B Neuropsychiatr Genet 168B:36–44PubMedCrossRefGoogle Scholar
  315. Smith ZD, Chan MM, Humm KC, Karnik R, Mekhoubad S, Regev A, Eggan K, Meissner A (2014) DNA methylation dynamics of the human preimplantation embryo. Nature 511:611–615PubMedPubMedCentralCrossRefGoogle Scholar
  316. Smith ZD, Chan MM, Mikkelsen TS, Gu H, Gnirke A, Regev A, Meissner A (2012) A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature 484:339–344PubMedPubMedCentralCrossRefGoogle Scholar
  317. Smith ZD, Meissner A (2013a) DNA methylation: roles in mammalian development. Nat Rev Genet 14:204–220PubMedCrossRefGoogle Scholar
  318. Smith ZD, Meissner A (2013b) The simplest explanation: passive DNA demethylation in PGCs. EMBO J 32:318–321PubMedPubMedCentralCrossRefGoogle Scholar
  319. Song J, Teplova M, Ishibe-Murakami S, Patel DJ (2012) Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation. Science 335:709–712PubMedPubMedCentralCrossRefGoogle Scholar
  320. Spruijt CG, Gnerlich F, Smits AH, Pfaffeneder T, Jansen PW, Bauer C, Munzel M, Wagner M, Muller M, Khan F, Eberl HC, Mensinga A, Brinkman AB, Lephikov K, Muller U, Walter J, Boelens R, Van Ingen H, Leonhardt H, Carell T, Vermeulen M (2013) Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives. Cell 152:1146–1159PubMedCrossRefGoogle Scholar
  321. Stewart KR, Veselovska L, Kelsey G (2016) Establishment and functions of DNA methylation in the germline. Epigenomics 8:1399–1413PubMedPubMedCentralCrossRefGoogle Scholar
  322. Suetake I, Shinozaki F, Miyagawa J, Takeshima H, Tajima S (2004) DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. J Biol Chem 279:27816–27823PubMedCrossRefGoogle Scholar
  323. Sweatt JD (2009) Experience-dependent epigenetic modifications in the central nervous system. Biol Psychiatry 65:191–197PubMedCrossRefGoogle Scholar
  324. Sweatt JD (2013) The emerging field of neuroepigenetics. Neuron 80:624–632PubMedCrossRefGoogle Scholar
  325. Syeda F, Fagan RL, Wean M, Avvakumov GV, Walker JR, Xue S, Dhe-Paganon S, Brenner C (2011) The replication focus targeting sequence (RFTS) domain is a DNA-competitive inhibitor of Dnmt1. J Biol Chem 286:15344–15351PubMedPubMedCentralCrossRefGoogle Scholar
  326. Szemes M, Dallosso AR, Melegh Z, Curry T, Li Y, Rivers C, Uney J, Magdefrau AS, Schwiderski K, Park JH, Brown KW, Shandilya J, Roberts SG, Malik K (2013) Control of epigenetic states by WT1 via regulation of de novo DNA methyltransferase 3A. Hum Mol Genet 22:74–83PubMedCrossRefGoogle Scholar
  327. Szenthe K, Nagy K, Buzas K, Niller HH, Minarovits J (2013) MicroRNAs as targets and tools in B-cell lymphoma therapy. J Canc Ther 4:466–474CrossRefGoogle Scholar
  328. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–935PubMedPubMedCentralCrossRefGoogle Scholar
  329. Takacs M, Segesdi J, Banati F, Koroknai A, Wolf H, Niller HH, Minarovits J (2009) The importance of epigenetic alterations in the development of Epstein-Barr virus-related lymphomas. Mediterr J Hematol Infect Dis 1:e2009012PubMedPubMedCentralGoogle Scholar
  330. Takebayashi S, Tamura T, Matsuoka C, Okano M (2007) Major and essential role for the DNA methylation mark in mouse embryogenesis and stable association of DNMT1 with newly replicated regions. Mol Cell Biol 27:8243–8258PubMedPubMedCentralCrossRefGoogle Scholar
  331. Tanaka Y, Kurumizaka H, Yokoyama S (2005) CpG methylation of the CENP-B box reduces human CENP-B binding. FEBS J 272:282–289PubMedCrossRefGoogle Scholar
  332. Tang YA, Lin RK, Tsai YT, Hsu HS, Yang YC, Chen CY, Wang YC (2012) MDM2 overexpression deregulates the transcriptional control of RB/E2F leading to DNA methyltransferase 3A overexpression in lung cancer. Clin Cancer Res 18:4325–4333PubMedCrossRefGoogle Scholar
  333. Taskin KM, Ozbilen A, Sezer F, Hurkan K, Gunes S (2016) Structure and expression of DNA methyltransferase genes from apomictic and sexual Boechera species. Comput Biol Chem 67:15–21PubMedCrossRefGoogle Scholar
  334. Termanis A, Torrea N, Culley J, Kerr A, Ramsahoye B, Stancheva I (2016) The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells. Nucleic Acids Res 44:7592–7604PubMedPubMedCentralCrossRefGoogle Scholar
  335. Termolino P, Cremona G, Consiglio MF, Conicella C (2016) Insights into epigenetic landscape of recombination-free regions. Chromosoma 125:301–308PubMedPubMedCentralCrossRefGoogle Scholar
  336. Thomson JP, Skene PJ, Selfridge J, Clouaire T, Guy J, Webb S, Kerr AR, Deaton A, Andrews R, James KD, Turner DJ, Illingworth R, Bird A (2010) CpG islands influence chromatin structure via the CpG-binding protein Cfp1. Nature 464:1082–1086PubMedPubMedCentralCrossRefGoogle Scholar
  337. Tollefsbol TO (2012) Epigenetics in human disease. Academic, WalthamCrossRefGoogle Scholar
  338. Tsai CL, Tainer JA (2013) Probing DNA by 2-OG-dependent dioxygenase. Cell 155:1448–1450PubMedPubMedCentralCrossRefGoogle Scholar
  339. Tsumura A, Hayakawa T, Kumaki Y, Takebayashi S, Sakaue M, Matsuoka C, Shimotohno K, Ishikawa F, Li E, Ueda HR, Nakayama J, Okano M (2006) Maintenance of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. Genes Cells 11:805–814PubMedCrossRefGoogle Scholar
  340. Tucker KL, Beard C, Dausmann J, Jackson-Grusby L, Laird PW, Lei H, Li E, Jaenisch R (1996) Germ-line passage is required for establishment of methylation and expression patterns of imprinted but not of nonimprinted genes. Genes Dev 10:1008–1020PubMedCrossRefGoogle Scholar
  341. Unoki M, Nakamura Y (2003) Methylation at CpG islands in intron 1 of EGR2 confers enhancer-like activity. FEBS Lett 554:67–72PubMedCrossRefGoogle Scholar
  342. Velasco G, Hube F, Rollin J, Neuillet D, Philippe C, Bouzinba-Segard H, Galvani A, Viegas-Pequignot E, Francastel C (2010) Dnmt3b recruitment through E2F6 transcriptional repressor mediates germ-line gene silencing in murine somatic tissues. Proc Natl Acad Sci U S A 107:9281–9286PubMedPubMedCentralCrossRefGoogle Scholar
  343. Vidalis A, Zivkovic D, Wardenaar R, Roquis D, Tellier A, Johannes F (2016) Methylome evolution in plants. Genome Biol 17:264PubMedPubMedCentralCrossRefGoogle Scholar
  344. Vlachogiannis G, Niederhuth CE, Tuna S, Stathopoulou A, Viiri K, De Rooij DG, Jenner RG, Schmitz RJ, Ooi SK (2015) The Dnmt3L ADD domain controls cytosine methylation establishment during spermatogenesis. Cell Rep 10:944–956.
  345. Von Meyenn F, Berrens RV, Andrews S, Santos F, Collier AJ, Krueger F, Osorno R, Dean W, Rugg-Gunn PJ, Reik W (2016) Comparative principles of DNA methylation reprogramming during human and mouse in vitro primordial germ cell specification. Dev Cell 39:104–115CrossRefGoogle Scholar
  346. Von Meyenn F, Reik W (2015) Forget the parents: epigenetic reprogramming in human germ cells. Cell 161:1248–1251CrossRefGoogle Scholar
  347. Vu TM, Nakamura M, Calarco JP, Susaki D, Lim PQ, Kinoshita T, Higashiyama T, Martienssen RA, Berger F (2013) RNA-directed DNA methylation regulates parental genomic imprinting at several loci in Arabidopsis. Development 140:2953–2960PubMedPubMedCentralCrossRefGoogle Scholar
  348. Waldminghaus T, Weigel C, Skarstad K (2012) Replication fork movement and methylation govern SeqA binding to the Escherichia coli chromosome. Nucleic Acids Res 40:5465–5476PubMedPubMedCentralCrossRefGoogle Scholar
  349. Walsh TK, Brisson JA, Robertson HM, Gordon K, Jaubert-Possamai S, Tagu D, Edwards OR (2010) A functional DNA methylation system in the pea aphid, Acyrthosiphon pisum. Insect Mol Biol 19(Suppl 2):215–228PubMedCrossRefGoogle Scholar
  350. Walter M, Teissandier A, Perez-Palacios R, Bourc’his D (2016) An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells. elife 5:e11418Google Scholar
  351. Walton EL, Francastel C, Velasco G (2014) Dnmt3b prefers germ line genes and centromeric regions: lessons from the ICF syndrome and cancer and implications for diseases. Biology (Basel) 3:578–605Google Scholar
  352. Wang KY, Chen CC, Tsai SF, Shen CJ (2016) Epigenetic enhancement of the post-replicative DNA mismatch repair of mammalian genomes by a hemi-mCpG-Np95-dnmt1 axis. Sci Rep 6:37490PubMedPubMedCentralCrossRefGoogle Scholar
  353. Watanabe T, Tomizawa S, Mitsuya K, Totoki Y, Yamamoto Y, Kuramochi-Miyagawa S, Iida N, Hoki Y, Murphy PJ, Toyoda A, Gotoh K, Hiura H, Arima T, Fujiyama A, Sado T, Shibata T, Nakano T, Lin H, Ichiyanagi K, Soloway PD, Sasaki H (2011) Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science 332:848–852PubMedPubMedCentralCrossRefGoogle Scholar
  354. Weaver IC, Cervoni N, Champagne FA, D’alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854PubMedCrossRefGoogle Scholar
  355. Weigele P, Raleigh EA (2016) Biosynthesis and function of modified bases in bacteria and their viruses. Chem Rev 116:12655–12687PubMedCrossRefGoogle Scholar
  356. Wiehle L, Raddatz G, Musch T, Dawlaty MM, Jaenisch R, Lyko F, Breiling A (2015) Tet1 and Tet2 protect DNA methylation canyons against Hypermethylation. Mol Cell Biol 36:452–461PubMedCrossRefGoogle Scholar
  357. Will CL, Luhrmann R (2011) Spliceosome structure and function. Cold Spring Harb Perspect Biol 3:a003707Google Scholar
  358. Williams K, Christensen J, Pedersen MT, Johansen JV, Cloos PA, Rappsilber J, Helin K (2011) TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 473:343–348PubMedPubMedCentralCrossRefGoogle Scholar
  359. Wilson GG (1988) Type II restriction--modification systems. Trends Genet 4:314–318PubMedCrossRefGoogle Scholar
  360. Wion D, Casadesus J (2006) N6-methyl-adenine: an epigenetic signal for DNA-protein interactions. Nat Rev Microbiol 4:183–192PubMedPubMedCentralCrossRefGoogle Scholar
  361. Wong NC, Wong LH, Quach JM, Canham P, Craig JM, Song JZ, Clark SJ, Choo KH (2006) Permissive transcriptional activity at the centromere through pockets of DNA hypomethylation. PLoS Genet 2:e17PubMedPubMedCentralCrossRefGoogle Scholar
  362. Wu H, Zhang Y (2014) Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell 156:45–68PubMedPubMedCentralCrossRefGoogle Scholar
  363. Wyatt GR (1951) Recognition and estimation of 5-methylcytosine in nucleic acids. Biochem J 48:581–584PubMedPubMedCentralCrossRefGoogle Scholar
  364. Xu F, Mao C, Ding Y, Rui C, Wu L, Shi A, Zhang H, Zhang L, Xu Z (2010) Molecular and enzymatic profiles of mammalian DNA methyltransferases: structures and targets for drugs. Curr Med Chem 17:4052–4071PubMedPubMedCentralCrossRefGoogle Scholar
  365. Xu X, Tao Y, Gao X, Zhang L, Li X, Zou W, Ruan K, Wang F, Xu GL, Hu R (2016) A CRISPR-based approach for targeted DNA demethylation. Cell Discov 2:16009PubMedPubMedCentralCrossRefGoogle Scholar
  366. Yamagata K, Yamazaki T, Miki H, Ogonuki N, Inoue K, Ogura A, Baba T (2007) Centromeric DNA hypomethylation as an epigenetic signature discriminates between germ and somatic cell lineages. Dev Biol 312:419–426PubMedCrossRefGoogle Scholar
  367. Yanagisawa Y, Ito E, Yuasa Y, Maruyama K (2002) The human DNA methyltransferases DNMT3A and DNMT3B have two types of promoters with different CpG contents. Biochim Biophys Acta 1577:457–465PubMedCrossRefGoogle Scholar
  368. Yang DL, Zhang G, Tang K, Li J, Yang L, Huang H, Zhang H, Zhu JK (2016a) Dicer-independent RNA-directed DNA methylation in Arabidopsis. Cell Res 26:66–82PubMedCrossRefGoogle Scholar
  369. Yang J, Guo R, Wang H, Ye X, Zhou Z, Dan J, Wang H, Gong P, Deng W, Yin Y, Mao S, Wang L, Ding J, Li J, Keefe DL, Dawlaty MM, Wang J, Xu G, Liu L (2016b) Tet enzymes regulate telomere maintenance and chromosomal stability of mouse ESCs. Cell Rep 15:1809–1821PubMedCrossRefGoogle Scholar
  370. Yang YC, Tang YA, Shieh JM, Lin RK, Hsu HS, Wang YC (2014) DNMT3B overexpression by deregulation of FOXO3a-mediated transcription repression and MDM2 overexpression in lung cancer. J Thorac Oncol 9:1305–1315PubMedCrossRefGoogle Scholar
  371. Yoder JA, Walsh CP, Bestor TH (1997) Cytosine methylation and the ecology of intragenomic parasites. Trends Genet 13:335–340PubMedCrossRefGoogle Scholar
  372. Yu NK, Baek SH, Kaang BK (2011) DNA methylation-mediated control of learning and memory. Mol Brain 4:5PubMedPubMedCentralCrossRefGoogle Scholar
  373. Zabet NR, Catoni M, Prischi F, Paszkowski J (2017) Cytosine methylation at CpCpG sites triggers accumulation of non-CpG methylation in gene bodies. Nucleic Acids Res 45:3777–3784.
  374. Zamudio N, Bourc’his D (2010) Transposable elements in the mammalian germline: a comfortable niche or a deadly trap? Heredity (Edinb) 105:92–104CrossRefGoogle Scholar
  375. Zaret KS, Watts J, Xu J, Wandzioch E, Smale ST, Sekiya T (2008) Pioneer factors, genetic competence, and inductive signaling: programming liver and pancreas progenitors from the endoderm. Cold Spring Harb Symp Quant Biol 73:119–126PubMedPubMedCentralCrossRefGoogle Scholar
  376. Zelena D (2012) Co-regulation and epigenetic dysregulation in schizophrenia and bipolar disorder. In: Minarovits J, Niller HH (eds) Patho-epigenetics of disease. Springer, New York, pp 281–347CrossRefGoogle Scholar
  377. Zhang G, Huang H, Liu D, Cheng Y, Liu X, Zhang W, Yin R, Zhang D, Zhang P, Liu J, Li C, Liu B, Luo Y, Zhu Y, Zhang N, He S, He C, Wang H, Chen D (2015a) N6-methyladenine DNA modification in drosophila. Cell 161:893–906PubMedCrossRefGoogle Scholar
  378. Zhang H, Zhu JK (2011) RNA-directed DNA methylation. Curr Opin Plant Biol 14:142–147PubMedPubMedCentralCrossRefGoogle Scholar
  379. Zhang Y, Jurkowska R, Soeroes S, Rajavelu A, Dhayalan A, Bock I, Rathert P, Brandt O, Reinhardt R, Fischle W, Jeltsch A (2010) Chromatin methylation activity of Dnmt3a and Dnmt3a/3L is guided by interaction of the ADD domain with the histone H3 tail. Nucleic Acids Res 38:4246–4253PubMedPubMedCentralCrossRefGoogle Scholar
  380. Zhang ZM, Liu S, Lin K, Luo Y, Perry JJ, Wang Y, Song J (2015b) Crystal structure of human DNA methyltransferase 1. J Mol Biol 427:2520–2531PubMedPubMedCentralCrossRefGoogle Scholar
  381. Zhao J, Zhu Y, Yang J, Li L, Wu H, De Jager PL, Jin P, Bennett DA (2017) A genome-wide profiling of brain DNA hydroxymethylation in Alzheimer’s disease. Alzheimers Dement 13:674–688.
  382. Zhou Y, Song N, Li X, Han Y, Ren Z, Xu JX, Han YC, Li F, Jia X (2017) Changes in the methylation status of the Oct3/4, Nanog, and Sox2 promoters in stem cells during regeneration of rat tracheal epithelium after injury. Oncotarget 8:2984–2994PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Hans Helmut Niller
    • 1
  • Anett Demcsák
    • 2
  • Janos Minarovits
    • 2
  1. 1.Institute of Medical Microbiology and HygieneUniversity of RegensburgRegensburgGermany
  2. 2.Department of Oral Biology and Experimental Dental Research, Faculty of DentistryUniversity of SzegedSzegedHungary

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