Abstract
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.
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References
Adhikari S, Curtis PD (2016) DNA methyltransferases and epigenetic regulation in bacteria. FEMS Microbiol Rev 40:575–591
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 7:1496
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 18:225–233
Anacker C, O’Donnell KJ, Meaney MJ (2014) Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function. Dialogues Clin Neurosci 16:321–333
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 13:229–232
Aran D, Sabato S, Hellman A (2013) DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes. Genome Biol 14:R21
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:e1006499
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:e9937
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 15:181–188
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 289:23882–23892
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 23:1224–1236
Bale TL (2015) Epigenetic and transgenerational reprogramming of brain development. Nat Rev Neurosci 16:332–344
Barlow DP, Bartolomei MS (2014) Genomic imprinting in mammals. Cold Spring Harb Perspect Biol 6:a018382
Bartolomei MS, Ferguson-Smith AC (2011) Mammalian genomic imprinting. Cold Spring Harb Perspect Biol 3:a002592
Becker C, Hagmann J, Muller J, Koenig D, Stegle O, Borgwardt K, Weigel D (2011) Spontaneous epigenetic variation in the Arabidopsis thaliana methylome. Nature 480:245–249
Bell AC, Felsenfeld G (2000) Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf 2 gene. Nature 405:482–485
Bell CG, Wilson GA, Beck S (2014) Human-specific CpG ‘beacons’ identify human-specific prefrontal cortex H3K4me3 chromatin peaks. Epigenomics 6:21–31
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 7:1188–1199
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 35:1961–1972
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 289:379–386
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 326:179–187
Bestor TH (2000) The DNA methyltransferases of mammals. Hum Mol Genet 9:2395–2402
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 112:6796–6799
Bheemanaik S, Reddy YV, Rao DN (2006) Structure, function and mechanism of exocyclic DNA methyltransferases. Biochem J 399:177–190
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 36:1099–1104
Bianchi C, Zangi R (2014) Dual base-flipping of cytosines in a CpG dinucleotide sequence. Biophys Chem 187-188:14–22
Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21
Bird AP (1986) CpG-rich islands and the function of DNA methylation. Nature 321:209–213
Bird AP (1987) CpG islands as gene markers in the vertebrate nucleus. Trends Genet 3:342–347
Blattler A, Farnham PJ (2013) Cross-talk between site-specific transcription factors and DNA methylation states. J Biol Chem 288:34287–34294
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:e1005854
Bogdanovic O, Veenstra GJ (2009) DNA methylation and methyl-CpG binding proteins: developmental requirements and function. Chromosoma 118:549–565
Bohacek J, Mansuy IM (2015) Molecular insights into transgenerational non-genetic inheritance of acquired behaviours. Nat Rev Genet 16:641–652
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 69:55–66
Brockdorff N (2013) Noncoding RNA and Polycomb recruitment. RNA 19:429–442
Brockdorff N, Turner BM (2015) Dosage compensation in mammals. Cold Spring Harb Perspect Biol 7:a019406
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 43–69
Cano-Rodriguez D, Rots MG (2016) Epigenetic editing: on the verge of reprogramming gene expression at will. Curr Genet Med Rep 4:170–179
Casadesus J (2016) Bacterial DNA methylation and Methylomes. Adv Exp Med Biol 945:35–61
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 3:160090
Cerase A, Pintacuda G, Tattermusch A, Avner P (2015) Xist localization and function: new insights from multiple levels. Genome Biol 16:166
Chaligne R, Heard E (2014) X-chromosome inactivation in development and cancer. FEBS Lett 588:2514–2522
Champagne FA, Curley JP (2009) Epigenetic mechanisms mediating the long-term effects of maternal care on development. Neurosci Biobehav Rev 33:593–600
Chen BF, Chan WY (2014) The de novo DNA methyltransferase DNMT3A in development and cancer. Epigenetics 9:669–677
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 354:468–472
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 351:397–400
Chen Q, Yan W, Duan E (2016c) Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications. Nat Rev Genet 17:733–743
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.
Chen T, Tsujimoto N, Li E (2004) The PWWP domain of Dnmt3a and Dnmt3b is required for directing DNA methylation to the major satellite repeats at pericentric heterochromatin. Mol Cell Biol 24:9048–9058
Chen Y, Damayanti NP, Irudayaraj J, Dunn K, Zhou FC (2014) Diversity of two forms of DNA methylation in the brain. Front Genet 5:46
Cheng X, Blumenthal RM (2011) Introduction–epiphanies in epigenetics. Prog Mol Biol Transl Sci 101:1–21
Cheng Y, Bernstein A, Chen D, Jin P (2015) 5-Hydroxymethylcytosine: a new player in brain disorders? Exp Neurol 268:3–9
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 31:16619–16636
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 39:104–118
Clark AT (2015) DNA methylation remodeling in vitro and in vivo. Curr Opin Genet Dev 34:82–87
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 48:581–586
Colot V, Rossignol JL (1999) Eukaryotic DNA methylation as an evolutionary device. BioEssays 21:402–411
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 4:406–410
Csankovszki G, Nagy A, Jaenisch R (2001) Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation. J Cell Biol 153:773–784
Dabe EC, Sanford RS, Kohn AB, Bobkova Y, Moroz LL (2015) DNA methylation in basal metazoans: insights from ctenophores. Integr Comp Biol 55:1096–1110
Damelin M, Bestor TH (2007) Biological functions of DNA methyltransferase 1 require its methyltransferase activity. Mol Cell Biol 27:3891–3899
Dan J, Chen T (2016) Genetic studies on mammalian DNA methyltransferases. Adv Exp Med Biol 945:123–150
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:R43
Davis HP, Squire LR (1984) Protein synthesis and memory: a review. Psychol Bull 96:518–559
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 29:102–111
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 100:13988–13993
Dean W (2014) DNA methylation and demethylation: a pathway to gametogenesis and development. Mol Reprod Dev 81:113–125
Deaton AM, Bird A (2011) CpG islands and the regulation of transcription. Genes Dev 25:1010–1022
Dekker AD, De Deyn PP, Rots MG (2014) Epigenetics: the neglected key to minimize learning and memory deficits in down syndrome. Neurosci Biobehav Rev 45:72–84
Delatte B, Deplus R, Fuks F (2014) Playing TETris with DNA modifications. EMBO J 33:1198–1211
Delgado-Morales R, Esteller M (2017) Opening up the DNA methylome of dementia. Mol Psychiatry 22:485–496. doi:10.1038/mp.2016.242
Denis H, Ndlovu MN, Fuks F (2011) Regulation of mammalian DNA methyltransferases: a route to new mechanisms. EMBO Rep 12:647–656
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 8:743–753
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 32:645–655
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 42:8285–8296
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 285:26114–26120
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 20:2195–2203
Dias BG, Ressler KJ (2014) Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci 17:89–96
Du Q, Wang Z, Schramm VL (2016) Human DNMT1 transition state structure. Proc Natl Acad Sci U S A 113:2916–2921
Duymich CE, Charlet J, Yang X, Jones PA, Liang G (2016) DNMT3B isoforms without catalytic activity stimulate gene body methylation as accessory proteins in somatic cells. Nat Commun 7:11453
Easwaran HP, Schermelleh L, Leonhardt H, Cardoso MC (2004) Replication-independent chromatin loading of Dnmt1 during G2 and M phases. EMBO Rep 5:1181–1186
Eden A, Gaudet F, Waghmare A, Jaenisch R (2003) Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300:455
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 7:157
Eggermann T (2012) Imprinting disorders. In: Minarovits J, Niller HH (eds) Patho-epigenetics of disease. Springer, New York, pp 379–395
Ehrlich M, Wilson GG, Kuo KC, Gehrke CW (1987) N4-methylcytosine as a minor base in bacterial DNA. J Bacteriol 169:939–943
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 140:383–394
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 341:1237973
Erwin JA, Marchetto MC, Gage FH (2014) Mobile DNA elements in the generation of diversity and complexity in the brain. Nat Rev Neurosci 15:497–506
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 19:1583–1591
Evsikov AV, Marin De Evsikova C (2016) Friend or foe: epigenetic regulation of retrotransposons in mammalian oogenesis and early development. Yale J Biol Med 89:487–497
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 19:808–822
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 10:1386–1397
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:e1000116
Fatemi M, Hermann A, Gowher H, Jeltsch A (2002) Dnmt3a and Dnmt1 functionally cooperate during de novo methylation of DNA. Eur J Biochem 269:4981–4984
Feng S, Jacobsen SE, Reik W (2010) Epigenetic reprogramming in plant and animal development. Science 330:622–627
Ficz G (2015) New insights into mechanisms that regulate DNA methylation patterning. J Exp Biol 218:14–20
Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH (2007) Recovery of learning and memory is associated with chromatin remodelling. Nature 447:178–182
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 529:110–114
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 2:160–169
Frank D, Keshet I, Shani M, Levine A, Razin A, Cedar H (1991) Demethylation of CpG islands in embryonic cells. Nature 351:239–241
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 326:241–251
Fritz EL, Papavasiliou FN (2010) Cytidine deaminases: AIDing DNA demethylation? Genes Dev 24:2107–2114
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 89:1827–1831
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 36:1094–1102
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 161:879–892
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 278:24132–24138
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 17:667–669
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 15–41
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 300:489–492
Georgia S, Kanji M, Bhushan A (2013) DNMT1 represses p53 to maintain progenitor cell survival during pancreatic organogenesis. Genes Dev 27:372–377
Gifford WD, Pfaff SL, Macfarlan TS (2013) Transposable elements as genetic regulatory substrates in early development. Trends Cell Biol 23:218–226
Gilbert SL, Pehrson JR, Sharp PA (2000) XIST RNA associates with specific regions of the inactive X chromatin. J Biol Chem 275:36491–36494
Gilbert SL, Sharp PA (1999) Promoter-specific hypoacetylation of X-inactivated genes. Proc Natl Acad Sci U S A 96:13825–13830
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 23:1590–1600
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 45:814–825
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 114:1928–1933
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 518:365–369
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 311:395–398
Goodier JL (2016) Restricting retrotransposons: a review. Mob DNA 7:16
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 18:3178–3193
Gopalakrishnan S, Van Emburgh BO, Robertson KD (2008) DNA methylation in development and human disease. Mutat Res 647:30–38
Gordon CA, Hartono SR, Chedin F (2013) Inactive DNMT3B splice variants modulate de novo DNA methylation. PLoS One 8:e69486
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 56:39–44
Grammatikakis I, Abdelmohsen K, Gorospe M (2017) Posttranslational control of HuR function. Wiley Interdiscip Rev RNA 8:e1372
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 17:150
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 161:868–878
Grigorenko EL, Kornilov SA, Naumova OY (2016) Epigenetic regulation of cognition: a circumscribed review of the field. Dev Psychopathol 28:1285–1304
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 111:483–493
Guibert S, Forne T, Weber M (2012) Global profiling of DNA methylation erasure in mouse primordial germ cells. Genome Res 22:633–641
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 161:1437–1452
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 10:645–659
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 23:2126–2135
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 14:1345–1351
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 517:640–644
Gyory I, Minarovits J (2005) Epigenetic regulation of lymphoid specific gene sets. Biochem Cell Biol 83:286–295
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 139:3623–3632
Hackett JA, Surani MA (2013) DNA methylation dynamics during the mammalian life cycle. Philos Trans R Soc Lond Ser B Biol Sci 368:20110328
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 19:48–54
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 24:177–184
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 8:20
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 405:486–489
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 455:826–829
He XJ, Chen T, Zhu JK (2011) Regulation and function of DNA methylation in plants and animals. Cell Res 21:442–465
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 279:48350–48359
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 7:5
Hervouet E, Vallette FM, Cartron PF (2009) Dnmt3/transcription factor interactions as crucial players in targeted DNA methylation. Epigenetics 4:487–499
Hervouet E, Vallette FM, Cartron PF (2010) Dnmt1/transcription factor interactions: an alternative mechanism of DNA methylation inheritance. Genes Cancer 1:434–443
Heyn H, Esteller M (2015) An adenine code for DNA: a second life for N6-methyladenine. Cell 161:710–713
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 109:10522–10527
Hoffmann A, Ziller M, Spengler D (2016) The future is the past: methylation QTLs in schizophrenia. Genes (Basel) 7:E104
Holliday R, Pugh JE (1975) DNA modification mechanisms and gene activity during development. Science 187:226–232
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) 7:294–306
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:R97
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 26:304–319
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 27:404–408
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 104:829–838
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 17:88
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 32:5019–5028
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 7:1556
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 22:6781–6789
Iida T, Suetake I, Tajima S, Morioka H, Ohta S, Obuse C, Tsurimoto T (2002) PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimethylated DNA. Genes Cells 7:997–1007
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 17:325–342
Iyer LM, Abhiman S, Aravind L (2011) Natural history of eukaryotic DNA methylation systems. Prog Mol Biol Transl Sci 101:25–104
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 19:40–47
Jeltsch A (2006) On the enzymatic properties of Dnmt1: specificity, processivity, mechanism of linear diffusion and allosteric regulation of the enzyme. Epigenetics 1:63–66
Jeltsch A (2013) Oxygen, epigenetic signaling, and the evolution of early life. Trends BiochemSci 38:172–176
Jeltsch A, Jurkowska RZ (2016) Allosteric control of mammalian DNA methyltransferases – a new regulatory paradigm. Nucleic Acids Res 44:8556–8575
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 5:8567
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 29:5366–5376
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 27:5967–5975
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 10:1749–1752
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 467:338–342
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 449:248–251
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 6:2998–3014
Jin B, Li Y, Robertson KD (2011) DNA methylation: superior or subordinate in the epigenetic hierarchy? Genes Cancer 2:607–617
Jin B, Robertson KD (2013) DNA methyltransferases, DNA damage repair, and cancer. Adv Exp Med Biol 754:3–29
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 385:557–564
Joh RI, Palmieri CM, Hill IT, Motamedi M (2014) Regulation of histone methylation by noncoding RNAs. Biochim Biophys Acta 1839:1385–1394
Jones PA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13:484–492
Jones PA, Liang G (2009) Rethinking how DNA methylation patterns are maintained. NatRevGenet 10:805–811
Jones PA, Takai D (2001) The role of DNA methylation in mammalian epigenetics. Science 293:1068–1070
Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J, Wolffe AP (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19:187–191
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:e1004345
Jurkowska RZ, Jeltsch A (2016) Enzymology of mammalian DNA methyltransferases. Adv Exp Med Biol 945:87–122
Jurkowski TP, Jeltsch A (2011) On the evolutionary origin of eukaryotic DNA methyltransferases and Dnmt2. PLoSOne 6:e28104
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 79:1086–1093
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 69:125–129
Kang J, Kalantry S, Rao A (2013) PGC7, H3K9me2 and Tet3: regulators of DNA methylation in zygotes. Cell Res 23:6–9
Keil KP, Vezina CM (2015) DNA methylation as a dynamic regulator of development and disease processes: spotlight on the prostate. Epigenomics 7:413–425
Kelley RI (1973) Isolation of a histone IIb1-IIb2 complex. Biochem Biophys Res Commun 54:1588–1594
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 368:20110336
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 19:1037–1043
Kim-Ha J, Kim YJ (2016) Age-related epigenetic regulation in the brain and its role in neuronal diseases. BMB Rep 49:671–680
Kim S, Kaang BK (2017) Epigenetic regulation and chromatin remodeling in learning and memory. Exp Mol Med 49:e281
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 269:2961–2970
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 227–280
Klein HU, De Jager PL (2016) Uncovering the role of the Methylome in dementia and neurodegeneration. Trends Mol Med 22:687–700
Kornberg RD (1974) Chromatin structure: a repeating unit of histones and DNA. Science 184:868–871
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 23:24–30
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 38:879–887
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 311:884–890
Kriaucionis S, Heintz N (2009) The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324:929–930
Kunnath L, Locker J (1982) Variable methylation of the ribosomal RNA genes of the rat. Nucleic Acids Res 10:3877–3892
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 103:10684–10689
Labrie V, Pai S, Petronis A (2012) Epigenetics of major psychosis: progress, problems and perspectives. Trends Genet 28:427–435
Lahiri DK, Maloney B, Zawia NH (2009) The LEARn model: an epigenetic explanation for idiopathic neurobiological diseases. Mol Psychiatry 14:992–1003
Li E, Beard C, Jaenisch R (1993) Role for DNA methylation in genomic imprinting. Nature 366:362–365
Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–926
Li E, Zhang Y (2014) DNA methylation in mammals. Cold Spring Harb Perspect Biol 6:a019133
Li N, Shen Q, Hua J (2016) Epigenetic Remodeling in Male Germline Development. Stem Cells Int 2016:3152173
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 111:7120–7125
Liang G, Chan MF, Tomigahara Y, Tsai YC, Gonzales FA, Li E, Laird PW, Jones PA (2002) Cooperativity between DNA methyltransferases in the maintenance methylation of repetitive elements. Mol Cell Biol 22:480–491
Lin RK, Wang YC (2014) Dysregulated transcriptional and post-translational control of DNA methyltransferases in cancer. Cell Biosci 4:46
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 70:5807–5817
Lin S, Gregory RI (2015) MicroRNA biogenesis pathways in cancer. Nat Rev Cancer 15:321–333
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 341:1237905
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 462:315–322
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 7:13052
Liu Y, Li X (2012) Darwin’s pangenesis and molecular medicine. Trends Mol Med 18:506–508
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 37:2658–2671
Lubin FD, Roth TL, Sweatt JD (2008) Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J Neurosci 28:10576–10586
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 17:3369–3384
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 487:57–63
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 20:332–340
Makarova KS, Wolf YI, Koonin EV (2013) Comparative genomics of defense systems in archaea and bacteria. Nucleic Acids Res 41:4360–4377
Maloney B, Lahiri DK (2016) Epigenetics of dementia: understanding the disease as a transformation rather than a state. Lancet Neurol 15:760–774
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 297:293–300
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 35:335–355
Marino-Ramirez L, Kann MG, Shoemaker BA, Landsman D (2005) Histone structure and nucleosome stability. Expert Rev Proteomics 2:719–729
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 302:890–893
Maunakea AK, Chepelev I, Cui K, Zhao K (2013) Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition. Cell Res 23:1256–1269
McCabe MT, Davis JN, Day ML (2005) Regulation of DNA methyltransferase 1 by the pRb/E2F1 pathway. Cancer Res 65:3624–3632
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 33:2947–2959
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 11:604–617
Messerschmidt DM, Knowles BB, Solter D (2014) DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev 28:812–828
Meyer KD, Jaffrey SR (2016) Expanding the diversity of DNA base modifications with N(6)-methyldeoxyadenosine. Genome Biol 17:5
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 13:664–666
Miller CA, Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53:857–869
Minarovits J, Banati F, Szenthe K, Niller HH (2016) Epigenetic regulation. Adv Exp Med Biol 879:1–25
Minarovits J, Niller HH (2012) Patho-epigenetics of disease. Springer, New York
Minarovits J, Niller HH (2016) Patho-epigenetics of infectious disease. Springer, New York
Minarovits J, Niller HH (2017) Current Trends and alternative scenarios in EBV research. Methods Mol Biol 1532:1–32
Miousse IR, Koturbash I (2015) The fine LINE: methylation drawing the cancer landscape. Biomed Res Int 2015:131547
Moll UM, Petrenko O (2003) The MDM2-p53 interaction. Mol Cancer Res 1:1001–1008
Monti B, Polazzi E, Contestabile A (2009) Biochemical, molecular and epigenetic mechanisms of valproic acid neuroprotection. Curr Mol Pharmacol 2:95–109
Moore LD, Le T, Fan G (2013) DNA methylation and its basic function. Neuropsychopharmacology 38:23–38
Morgan HD, Santos F, Green K, Dean W, Reik W (2005) Epigenetic reprogramming in mammals. Hum Mol Genet 14(1):R47–R58
Moroz LL, Kohn AB (2013) Single-neuron transcriptome and methylome sequencing for epigenomic analysis of aging. Methods Mol Biol 1048:323–352
Munoz-Lopez M, Garcia-Perez JL (2010) DNA transposons: nature and applications in genomics. Curr Genomics 11:115–128
Muotri AR, Marchetto MC, Coufal NG, Oefner R, Yeo G, Nakashima K, Gage FH (2010) L1 retrotransposition in neurons is modulated by MeCP2. Nature 468:443–446
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 486:415–419
Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393:386–389
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:e1000739
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 280:38914–38922
Nikolova YS, Hariri AR (2015) Can we observe epigenetic effects on human brain function? Trends Cogn Sci 19:366–373
Ogden GB, Pratt MJ, Schaechter M (1988) The replicative origin of the E. coli chromosome binds to cell membranes only when hemimethylated. Cell 54:127–135
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 17:76
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 77:246–255
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 131:1287–1300
Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257
Oliveira AM, Hemstedt TJ, Bading H (2012) Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities. Nat Neurosci 15:1111–1113
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 26:5553–5563
Pandya-Jones A, Plath K (2016) The "lnc" between 3D chromatin structure and X chromosome inactivation. Semin Cell Dev Biol 56:35–47
Pearson CE, Nichol Edamura K, Cleary JD (2005) Repeat instability: mechanisms of dynamic mutations. Nat Rev Genet 6:729–742
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 7:597–606
Peterson EJ, Bogler O, Taylor SM (2003) p53-mediated repression of DNA methyltransferase 1 expression by specific DNA binding. Cancer Res 63:6579–6582
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 20:861–874
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 10:574–581
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 14:696–706
Posfai J, Bhagwat AS, Posfai G, Roberts RJ (1989) Predictive motifs derived from cytosine methyltransferases. Nucleic Acids Res 17:2421–2435
Pradhan S, Bacolla A, Wells RD, Roberts RJ (1999) Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. J Biol Chem 274:33002–33010
Putiri EL, Robertson KD (2011) Epigenetic mechanisms and genome stability. Clin Epigenetics 2:299–314
Qin W, Leonhardt H, Pichler G (2011) Regulation of DNA methyltransferase 1 by interactions and modifications. Nucleus 2:392–402
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 2:766–773
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 149:693–707
Rasmussen KD, Helin K (2016) Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev 30:733–750
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 245:304–314
Rebhandl S, Huemer M, Greil R, Geisberger R (2015) AID/APOBEC deaminases and cancer. Oncoscience 2:320–333
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 39:1749–1762
Reik W (2007) Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447:425–432
Reik W, Walter J (1998) Imprinting mechanisms in mammals. Curr Opin Genet Dev 8:154–164
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 368:20120151
Riggs AD (1975) X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet 14:9–25
Robertson KD (2001) DNA methylation, methyltransferases, and cancer. Oncogene 20:3139–3155
Rodriguez-Osorio N, Wang H, Rupinski J, Bridges SM, Memili E (2010) Comparative functional genomics of mammalian DNA methyltransferases. Reprod Biomed Online 20:243–255
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 10:557–560
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 79:1109–1122
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 7:26
Saitou M, Yamaji M (2012) Primordial germ cells in mice. Cold Spring Harb Perspect Biol 4:a008375
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 282:16391–16400
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. doi:10.1002/syn.21959
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:e718
Sasaki H, Ishihara K, Kato R (2000) Mechanisms of Igf2/H19 imprinting: DNA methylation, chromatin and long-distance gene regulation. J Biochem 127:711–715
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:e54710
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 16:21
Schizophrenia Working Group of the Psychiatric Genomics, Consortium (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511:421–427
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 592:110–118
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 41:4860–4876
Schrader A, Gross T, Thalhammer V, Langst G (2015) Characterization of Dnmt1 binding and DNA methylation on nucleosomes and nucleosomal arrays. PLoS One 10:e0140076
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 523:212–216
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 46:199–203
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 20:699–708
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 368:20110330
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 25:281–288
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 21:555–565
Shabbir MA, Hao H, Shabbir MZ, Wu Q, Sattar A, Yuan Z (2016) Bacteria vs. bacteriophages: parallel evolution of immune arsenals. Front Microbiol 7:1292
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 21:1592–1600
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 479:74–79
Shukla S, Oberdoerffer S (2012) Co-transcriptional regulation of alternative pre-mRNA splicing. Biochim Biophys Acta 1819:673–683
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 20:1201–1215
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 19:581–589
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 11:817–820
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 7:8
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:36–44
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 511:611–615
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 484:339–344
Smith ZD, Meissner A (2013a) DNA methylation: roles in mammalian development. Nat Rev Genet 14:204–220
Smith ZD, Meissner A (2013b) The simplest explanation: passive DNA demethylation in PGCs. EMBO J 32:318–321
Song J, Teplova M, Ishibe-Murakami S, Patel DJ (2012) Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation. Science 335:709–712
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 152:1146–1159
Stewart KR, Veselovska L, Kelsey G (2016) Establishment and functions of DNA methylation in the germline. Epigenomics 8:1399–1413
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 279:27816–27823
Sweatt JD (2009) Experience-dependent epigenetic modifications in the central nervous system. Biol Psychiatry 65:191–197
Sweatt JD (2013) The emerging field of neuroepigenetics. Neuron 80:624–632
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 286:15344–15351
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 22:74–83
Szenthe K, Nagy K, Buzas K, Niller HH, Minarovits J (2013) MicroRNAs as targets and tools in B-cell lymphoma therapy. J Canc Ther 4:466–474
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 324:930–935
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:e2009012
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 27:8243–8258
Tanaka Y, Kurumizaka H, Yokoyama S (2005) CpG methylation of the CENP-B box reduces human CENP-B binding. FEBS J 272:282–289
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 18:4325–4333
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 67:15–21
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 44:7592–7604
Termolino P, Cremona G, Consiglio MF, Conicella C (2016) Insights into epigenetic landscape of recombination-free regions. Chromosoma 125:301–308
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 464:1082–1086
Tollefsbol TO (2012) Epigenetics in human disease. Academic, Waltham
Tsai CL, Tainer JA (2013) Probing DNA by 2-OG-dependent dioxygenase. Cell 155:1448–1450
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 11:805–814
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 10:1008–1020
Unoki M, Nakamura Y (2003) Methylation at CpG islands in intron 1 of EGR2 confers enhancer-like activity. FEBS Lett 554:67–72
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 107:9281–9286
Vidalis A, Zivkovic D, Wardenaar R, Roquis D, Tellier A, Johannes F (2016) Methylome evolution in plants. Genome Biol 17:264
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. doi:10.1016/j.celrep.2015.01.021
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 39:104–115
Von Meyenn F, Reik W (2015) Forget the parents: epigenetic reprogramming in human germ cells. Cell 161:1248–1251
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 140:2953–2960
Waldminghaus T, Weigel C, Skarstad K (2012) Replication fork movement and methylation govern SeqA binding to the Escherichia coli chromosome. Nucleic Acids Res 40:5465–5476
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):215–228
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:e11418
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) 3:578–605
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 6:37490
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 332:848–852
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 7:847–854
Weigele P, Raleigh EA (2016) Biosynthesis and function of modified bases in bacteria and their viruses. Chem Rev 116:12655–12687
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 36:452–461
Will CL, Luhrmann R (2011) Spliceosome structure and function. Cold Spring Harb Perspect Biol 3:a003707
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 473:343–348
Wilson GG (1988) Type II restriction–modification systems. Trends Genet 4:314–318
Wion D, Casadesus J (2006) N6-methyl-adenine: an epigenetic signal for DNA-protein interactions. Nat Rev Microbiol 4:183–192
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:e17
Wu H, Zhang Y (2014) Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell 156:45–68
Wyatt GR (1951) Recognition and estimation of 5-methylcytosine in nucleic acids. Biochem J 48:581–584
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 17:4052–4071
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 2:16009
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 312:419–426
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 1577:457–465
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 26:66–82
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 15:1809–1821
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 9:1305–1315
Yoder JA, Walsh CP, Bestor TH (1997) Cytosine methylation and the ecology of intragenomic parasites. Trends Genet 13:335–340
Yu NK, Baek SH, Kaang BK (2011) DNA methylation-mediated control of learning and memory. Mol Brain 4:5
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. doi:10.1093/nar/gkw1330
Zamudio N, Bourc’his D (2010) Transposable elements in the mammalian germline: a comfortable niche or a deadly trap? Heredity (Edinb) 105:92–104
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 73:119–126
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 281–347
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 161:893–906
Zhang H, Zhu JK (2011) RNA-directed DNA methylation. Curr Opin Plant Biol 14:142–147
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 38:4246–4253
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 427:2520–2531
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. doi:10.1016/j.jalz.2016.10.004
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 8:2984–2994
Acknowledgments
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.
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Niller, H.H., Demcsák, A., Minarovits, J. (2017). DNA Methylation in Eukaryotes: Regulation and Function. In: Krell, T. (eds) Cellular Ecophysiology of Microbe. Handbook of Hydrocarbon and Lipid Microbiology . Springer, Cham. https://doi.org/10.1007/978-3-319-20796-4_24-1
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