Enzymology of Mammalian DNA Methyltransferases

  • Renata Z. JurkowskaEmail author
  • Albert JeltschEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 945)


DNA methylation is currently one of the hottest topics in basic and biomedical research. Despite tremendous progress in understanding the structures and biochemical properties of the mammalian DNA nucleotide methyltransferases (DNMTs), principles of their regulation in cells have only begun to be uncovered. In mammals, DNA methylation is introduced by the DNMT1, DNMT3A, and DNMT3B enzymes, which are all large multi-domain proteins. These enzymes contain a catalytic C-terminal domain with a characteristic cytosine-C5 methyltransferase fold and an N-terminal part with different domains that interacts with other proteins and chromatin and is involved in targeting and regulation of the DNMTs. The subnuclear localization of the DNMT enzymes plays an important role in their biological function: DNMT1 is localized to replicating DNA via interaction with PCNA and UHRF1. DNMT3 enzymes bind to heterochromatin via protein multimerization and are targeted to chromatin by their ADD and PWWP domains. Recently, a novel regulatory mechanism has been discovered in DNMTs, as latest structural and functional data demonstrated that the catalytic activities of all three enzymes are under tight allosteric control of their N-terminal domains having autoinhibitory functions. This mechanism provides numerous possibilities for the precise regulation of the methyltransferases via controlling the binding and release of autoinhibitory domains by protein factors, noncoding RNAs, or by posttranslational modifications of the DNMTs. In this chapter, we summarize key enzymatic properties of DNMTs, including their specificity and processivity, and afterward we focus on the regulation of their activity and targeting via allosteric processes, protein interactors, and posttranslational modifications.


PWWP Domain Subnuclear Localization DNMT3 Protein DNMT3 Enzyme CXXC Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


ADD domain







Bromo-adjacent homology domain


Cytosine-guanine dinucleotide separated by a phosphate


DNA methyltransferase-associated protein 1


Differentially methylated region


(Mammalian) DNA nucleotide methyltransferase


Histone deacetylase

KG repeats

Lysine-glycine repeats




Methyl-binding domain








Non(protein)-coding RNA


Proliferating cell nuclear antigen


PCNA-binding domain


Plant homeodomain


Posttranslational modification


Replication foci-targeting domain


Sirtuin 1

SRA domain

SET- and RING-associated domain


Target recognition domain


Tandem Tudor domain


Ubiquitin-like with PHD and ring finger domains 1


Ubiquitin-specific peptidase 7


Zinc finger and homeobox protein 1


  1. Allis CD, Caparos M-L, Jenuwein T, Reinberg D. Epigenetics. 2nd ed. Woodbury: CSH Laboratory Press; 2015.Google Scholar
  2. Aoki A, Suetake I, Miyagawa J, Fujio T, Chijiwa T, Sasaki H, et al. Enzymatic properties of de novo-type mouse DNA (cytosine-5) methyltransferases. Nucleic Acids Res. 2001;29(17):3506–12.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Arand J, Spieler D, Karius T, Branco MR, Meilinger D, Meissner A, et al. In vivo control of CpG and non-CpG DNA methylation by DNA methyltransferases. PLoS Genet. 2012;8(6):e1002750.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Arita K, Ariyoshi M, Tochio H, Nakamura Y, Shirakawa M. Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism. Nature. 2008;455(7214):818–21.PubMedCrossRefGoogle Scholar
  5. Armstrong L. Epigenetics. New York: Garland Science; 2013.Google Scholar
  6. Avvakumov GV, Walker JR, Xue S, Li Y, Duan S, Bronner C, et al. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature. 2008;455(7214):822–5.PubMedCrossRefGoogle Scholar
  7. Bacolla A, Pradhan S, Roberts RJ, Wells RD. Recombinant human DNA (cytosine-5) methyltransferase. II. Steady-state kinetics reveal allosteric activation by methylated dna. J Biol Chem. 1999;274(46):33011–9.PubMedCrossRefGoogle Scholar
  8. Bacolla A, Pradhan S, Larson JE, Roberts RJ, Wells RD. Recombinant human DNA (cytosine-5) methyltransferase. III. Allosteric control, reaction order, and influence of plasmid topology and triplet repeat length on methylation of the fragile X CGG.CCG sequence. J Biol Chem. 2001;276(21):18605–13.PubMedCrossRefGoogle Scholar
  9. Ball MP, Li JB, Gao Y, Lee JH, LeProust EM, Park IH, et al. Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol. 2009;27(4):361–8.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129(4):823–37.PubMedCrossRefGoogle Scholar
  11. Bashtrykov P, Jankevicius G, Smarandache A, Jurkowska RZ, Ragozin S, Jeltsch A. Specificity of Dnmt1 for methylation of hemimethylated CpG sites resides in its catalytic domain. Chem Biol. 2012a;19(5):572–8.PubMedCrossRefGoogle Scholar
  12. Bashtrykov P, Ragozin S, Jeltsch A. Mechanistic details of the DNA recognition by the Dnmt1 DNA methyltransferase. FEBS Lett. 2012b;586(13):1821–3.PubMedCrossRefGoogle Scholar
  13. Bashtrykov P, Jankevicius G, Jurkowska RZ, Ragozin S, Jeltsch A. The UHRF1 protein stimulates the activity and specificity of the maintenance DNA methyltransferase DNMT1 by an allosteric mechanism. J Biol Chem. 2014a;289(7):4106–15.PubMedCrossRefGoogle Scholar
  14. Bashtrykov P, Rajavelu A, Hackner B, Ragozin S, Carell T, Jeltsch A. Targeted mutagenesis results in an activation of DNA methyltransferase 1 and confirms an autoinhibitory role of its RFTS domain. Chembiochem Eur J Chem Biol. 2014b;15(5):743–8.CrossRefGoogle Scholar
  15. Baubec T, Colombo DF, Wirbelauer C, Schmidt J, Burger L, Krebs AR, et al. Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. Nature. 2015;520(7546):243–7.PubMedCrossRefGoogle Scholar
  16. Baylin SB, Jones PA. A decade of exploring the cancer epigenome – biological and translational implications. Nat Rev Cancer. 2011;11(10):726–34.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Bergman Y, Cedar H. DNA methylation dynamics in health and disease. Nat Struct Mol Biol. 2013;20(3):274–81.PubMedCrossRefGoogle Scholar
  18. Berkyurek AC, Suetake I, Arita K, Takeshita K, Nakagawa A, Shirakawa M, et al. 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. 2014;289(1):379–86.PubMedCrossRefGoogle Scholar
  19. Bierhoff H, Schmitz K, Maass F, Ye J, Grummt I. Noncoding transcripts in sense and antisense orientation regulate the epigenetic state of ribosomal RNA genes. Cold Spring Harb Symp Quant Biol. 2010;75:357–64.PubMedCrossRefGoogle Scholar
  20. Bonasio R, Tu S, Reinberg D. Molecular signals of epigenetic states. Science. 2010;330(6004):612–6.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Bostick M, Kim JK, Esteve PO, Clark A, Pradhan S, Jacobsen SE. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science. 2007;317(5845):1760–4.PubMedCrossRefGoogle Scholar
  22. Bourc’his D, Bestor TH. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature. 2004;431(7004):96–9.PubMedCrossRefGoogle Scholar
  23. Bourc’his D, Xu GL, Lin CS, Bollman B, Bestor TH. Dnmt3L and the establishment of maternal genomic imprints. Science. 2001;294(5551):2536–9.PubMedCrossRefGoogle Scholar
  24. Brenner C, Deplus R, Didelot C, Loriot A, Vire E, De Smet C, et al. Myc represses transcription through recruitment of DNA methyltransferase corepressor. EMBO J. 2005;24(2):336–46.PubMedCrossRefGoogle Scholar
  25. Cai Y, Geutjes EJ, de Lint K, Roepman P, Bruurs L, Yu LR, et al. The NuRD complex cooperates with DNMTs to maintain silencing of key colorectal tumor suppressor genes. Oncogene. 2014;33(17):2157–68.PubMedCrossRefGoogle Scholar
  26. Chedin F, Lieber MR, Hsieh CL. The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a. Proc Natl Acad Sci U S A. 2002;99(26):16916–21.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Chen TP, Tsujimoto N, Li E. The PWWP domain of Dnmt3a and Dnmt3b is required for directing DNA methylation to the major satellite repeats at pericentric heterochromatin. Mol Cell Biol. 2004;24(20):9048–58.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Chen ZX, Mann JR, Hsieh CL, Riggs AD, Chedin F. Physical and functional interactions between the human DNMT3L protein and members of the de novo methyltransferase family. J Cell Biochem. 2005;95(5):902–17.PubMedCrossRefGoogle Scholar
  29. Chen L, Chen K, Lavery LA, Baker SA, Shaw CA, Li W, et al. MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome. Proc Natl Acad Sci U S A. 2015;112(17):5509–14.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Cheng X, Blumenthal RM. Mammalian DNA methyltransferases: a structural perspective. Structure. 2008;16(3):341–50.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Cheng X, Roberts RJ. AdoMet-dependent methylation, DNA methyltransferases and base flipping. Nucleic Acids Res. 2001;29(18):3784–95.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Cheng J, Yang H, Fang J, Ma L, Gong R, Wang P, et al. Molecular mechanism for USP7-mediated DNMT1 stabilization by acetylation. Nat Commun. 2015;6:7023.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009;325(5942):834–40.PubMedCrossRefGoogle Scholar
  34. Christman JK, Sheikhnejad G, Marasco CJ, Sufrin JR. 5-Methyl-2′-deoxycytidine in single-stranded DNA can act in cis to signal de novo DNA methylation. Proc Natl Acad Sci U S A. 1995;92(16):7347–51.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF. Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science. 1997;277(5334):1996–2000.PubMedCrossRefGoogle Scholar
  36. Datta J, Majumder S, Bai S, Ghoshal K, Kutay H, Smith DS, et al. Physical and functional interaction of DNA methyltransferase 3A with Mbd3 and Brg1 in mouse lymphosarcoma cells. Cancer Res. 2005;65(23):10891–900.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Deplus R, Blanchon L, Rajavelu A, Boukaba A, Defrance M, Luciani J, et al. Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a. Cell Rep. 2014;8(3):743–53.PubMedCrossRefGoogle Scholar
  38. Dhayalan A, Rajavelu A, Rathert P, Tamas R, Jurkowska RZ, Ragozin S, et al. The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation. J Biol Chem. 2010;285(34):26114–20.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Di Ruscio A, Ebralidze AK, Benoukraf T, Amabile G, Goff LA, Terragni J, et al. DNMT1-interacting RNAs block gene-specific DNA methylation. Nature. 2013;503(7476):371–6.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Du Z, Song J, Wang Y, Zhao Y, Guda K, Yang S, et al. DNMT1 stability is regulated by proteins coordinating deubiquitination and acetylation-driven ubiquitination. Sci Signal. 2010;3(146):ra80.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Du Q, Wang Z, Schramm VL. Human DNMT1 transition state structure. Proc Natl Acad Sci U S A. 2016;113(11):2916–21.Google Scholar
  42. Easwaran HP, Schermelleh L, Leonhardt H, Cardoso MC. Replication-independent chromatin loading of Dnmt1 during G2 and M phases. EMBO Rep. 2004;5(12):1181–6.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Eckhardt F, Lewin J, Cortese R, Rakyan VK, Attwood J, Burger M, et al. DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet. 2006;38(12):1378–85.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Edmunds JW, Mahadevan LC, Clayton AL. Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation. EMBO J. 2008;27(2):406–20.PubMedCrossRefGoogle Scholar
  45. Egger G, Jeong S, Escobar SG, Cortez CC, Li TW, Saito Y, et al. Identification of DNMT1 (DNA methyltransferase 1) hypomorphs in somatic knockouts suggests an essential role for DNMT1 in cell survival. Proc Natl Acad Sci U S A. 2006;103(38):14080–5.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Emperle M, Rajavelu A, Reinhardt R, Jurkowska RZ, Jeltsch A. Cooperative DNA binding and protein/DNA fiber formation increases the activity of the Dnmt3a DNA methyltransferase. J Biol Chem. 2014;289(43):29602–13.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, Epstein CB, et al. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature. 2011;473(7345):43–9.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Esteve PO, Chin HG, Benner J, Feehery GR, Samaranayake M, Horwitz GA, et al. Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells. Proc Natl Acad Sci U S A. 2009;106(13):5076–81.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Esteve PO, Chang Y, Samaranayake M, Upadhyay AK, Horton JR, Feehery GR, et al. A methylation and phosphorylation switch between an adjacent lysine and serine determines human DNMT1 stability. Nat Struct Mol Biol. 2011;18(1):42–8.PubMedCrossRefGoogle Scholar
  50. Esteve PO, Zhang G, Ponnaluri VK, Deepti K, Chin HG, Dai N, et al. Binding of 14-3-3 reader proteins to phosphorylated DNMT1 facilitates aberrant DNA methylation and gene expression. Nucleic Acids Res. 2016;44(4):1642–56.PubMedCrossRefGoogle Scholar
  51. Fatemi M, Hermann A, Pradhan S, Jeltsch A. The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA. J Mol Biol. 2001;309(5):1189–99.PubMedCrossRefGoogle Scholar
  52. Fatemi M, Hermann A, Gowher H, Jeltsch A. Dnmt3a and Dnmt1 functionally cooperate during de novo methylation of DNA. Eur J Biochemistry FEBS. 2002;269(20):4981–4.CrossRefGoogle Scholar
  53. Felle M, Hoffmeister H, Rothammer J, Fuchs A, Exler JH, Langst G. Nucleosomes protect DNA from DNA methylation in vivo and in vitro. Nucleic Acids Res. 2011;39(16):6956–69.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Flynn J, Fang JY, Mikovits JA, Reich NO. A potent cell-active allosteric inhibitor of murine DNA cytosine C5 methyltransferase. J Biol Chem. 2003;278(10):8238–43.PubMedCrossRefGoogle Scholar
  55. Fuks F, Burgers WA, Godin N, Kasai M, Kouzarides T. Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription. EMBO J. 2001;20(10):2536–44.PubMedPubMedCentralCrossRefGoogle Scholar
  56. Fuks F, Hurd PJ, Deplus R, Kouzarides T. The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res. 2003a;31(9):2305–12.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Fuks F, Hurd PJ, Wolf D, Nan X, Bird AP, Kouzarides T. The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem. 2003b;278(6):4035–40.PubMedCrossRefGoogle Scholar
  58. Gabel HW, Kinde B, Stroud H, Gilbert CS, Harmin DA, Kastan NR, et al. Disruption of DNA-methylation-dependent long gene repression in Rett syndrome. Nature. 2015;522(7554):89–93.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Ge YZ, Pu MT, Gowher H, Wu HP, Ding JP, Jeltsch A, et al. Chromatin targeting of de novo DNA methyltransferases by the PWWP domain. J Biol Chem. 2004;279(24):25447–54.PubMedCrossRefGoogle Scholar
  60. Geiman TM, Sankpal UT, Robertson AK, Zhao Y, Robertson KD. DNMT3B interacts with hSNF2H chromatin remodeling enzyme, HDACs 1 and 2, and components of the histone methylation system. Biochem Biophys Res Commun. 2004;318(2):544–55.PubMedCrossRefGoogle Scholar
  61. Glickman JF, Flynn J, Reich NO. Purification and characterization of recombinant baculovirus-expressed mouse DNA methyltransferase. Biochem Biophys Res Commun. 1997a;230(2):280–4.PubMedCrossRefGoogle Scholar
  62. Glickman JF, Pavlovich JG, Reich NO. Peptide mapping of the murine DNA methyltransferase reveals a major phosphorylation site and the start of translation. J Biol Chem. 1997b;272(28):17851–7.PubMedCrossRefGoogle Scholar
  63. Gowher H, Jeltsch A. Enzymatic properties of recombinant Dnmt3a DNA methyltransferase from mouse: the enzyme modifies DNA in a non-processive manner and also methylates non-CpA sites. J Mol Biol. 2001;309(5):1201–8.PubMedCrossRefGoogle Scholar
  64. Gowher H, Jeltsch A. Molecular enzymology of the catalytic domains of the Dnmt3a and Dnmt3b DNA methyltransferases. J Biol Chem. 2002;277(23):20409–14.PubMedCrossRefGoogle Scholar
  65. Gowher H, Liebert K, Hermann A, Xu G, Jeltsch A. Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L. J Biol Chem. 2005a;280(14):13341–8.PubMedCrossRefGoogle Scholar
  66. Gowher H, Stockdale CJ, Goyal R, Ferreira H, Owen-Hughes T, Jeltsch A. De novo methylation of nucleosomal DNA by the mammalian Dnmt1 and Dnmt3A DNA methyltransferases. Biochemistry. 2005b;44(29):9899–904.PubMedCrossRefGoogle Scholar
  67. Gowher H, Loutchanwoot P, Vorobjeva O, Handa V, Jurkowska RZ, Jurkowski TP, et al. Mutational analysis of the catalytic domain of the murine Dnmt3a DNA-(cytosine C5)-methyltransferase. J Mol Biol. 2006;357(3):928–41.PubMedCrossRefGoogle Scholar
  68. Goyal R, Reinhardt R, Jeltsch A. Accuracy of DNA methylation pattern preservation by the Dnmt1 methyltransferase. Nucleic Acids Res. 2006;34(4):1182–8.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Goyal R, Rathert P, Laser H, Gowher H, Jeltsch A. Phosphorylation of serine-515 activates the Mammalian maintenance methyltransferase Dnmt1. Epigenetics. 2007;2(3):155–60.PubMedCrossRefGoogle Scholar
  70. Guenther MG, Levine SS, Boyer LA, Jaenisch R, Young RA. A chromatin landmark and transcription initiation at most promoters in human cells. Cell. 2007;130(1):77–88.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Guo JU, Su Y, Shin JH, Shin J, Li H, Xie B, et al. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat Neurosci. 2014;17(2):215–22.PubMedCrossRefGoogle Scholar
  72. Guo X, Wang L, Li J, Ding Z, Xiao J, Yin X, et al. Structural insight into autoinhibition and histone H3-induced activation of DNMT3A. Nature. 2015;517(7536):640–4.PubMedCrossRefGoogle Scholar
  73. Hamidi T, Singh AK, Chen T. Genetic alterations of DNA methylation machinery in human diseases. Epigenomics. 2015;7(2):247–65.PubMedCrossRefGoogle Scholar
  74. Handa V, Jeltsch A. Profound flanking sequence preference of Dnmt3a and Dnmt3b mammalian DNA methyltransferases shape the human epigenome. J Mol Biol. 2005;348(5):1103–12.PubMedCrossRefGoogle Scholar
  75. Hashimoto H, Horton JR, Zhang X, Bostick M, Jacobsen SE, Cheng X. The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix. Nature. 2008;455(7214):826–9.PubMedPubMedCentralCrossRefGoogle Scholar
  76. Hata K, Okano M, Lei H, Li E. Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development. 2002;129(8):1983–93.PubMedGoogle Scholar
  77. Hellman A, Chess A. Gene body-specific methylation on the active X chromosome. Science. 2007;315(5815):1141–3.PubMedCrossRefGoogle Scholar
  78. Hermann A, Gowher H, Jeltsch A. Biochemistry and biology of mammalian DNA methyltransferases. Cell Mole Life Sci CMLS. 2004a;61(19–20):2571–87.CrossRefGoogle Scholar
  79. Hermann A, Goyal R, Jeltsch A. The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites. J Biol Chem. 2004b;279(46):48350–9.PubMedCrossRefGoogle Scholar
  80. Hervouet E, Lalier L, Debien E, Cheray M, Geairon A, Rogniaux H, et al. Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells. PLoS One. 2010;5(6):e11333.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Hodges E, Smith AD, Kendall J, Xuan Z, Ravi K, Rooks M, et al. High definition profiling of mammalian DNA methylation by array capture and single molecule bisulfite sequencing. Genome Res. 2009;19(9):1593–605.PubMedPubMedCentralCrossRefGoogle Scholar
  82. Holoch D, Moazed D. RNA-mediated epigenetic regulation of gene expression. Nat Rev Genet. 2015;16(2):71–84.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Holz-Schietinger C, Reich NO. The inherent processivity of the human de novo methyltransferase 3A (DNMT3A) is enhanced by DNMT3L. J Biol Chem. 2010;285(38):29091–100.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Holz-Schietinger C, Reich NO. RNA modulation of the human DNA methyltransferase 3A. Nucleic Acids Res. 2012;40(17):8550–7.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Hu L, Li Z, Wang P, Lin Y, Xu Y. Crystal structure of PHD domain of UHRF1 and insights into recognition of unmodified histone H3 arginine residue 2. Cell Res. 2011;21(9):1374–8.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Iida T, Suetake I, Tajima S, Morioka H, Ohta S, Obuse C, et al. PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimethylated DNA. Genes Cells Devoted Mole Cell Mech. 2002;7(10):997–1007.CrossRefGoogle Scholar
  87. Iwasaki YW, Siomi MC, Siomi H. PIWI-interacting RNA: its biogenesis and functions. Annu Rev Biochem. 2015;84:405–33.PubMedCrossRefGoogle Scholar
  88. Jeltsch A. Beyond Watson and Crick: DNA methylation and molecular enzymology of DNA methyltransferases. Chem Eur J Chem Biol. 2002;3(4):275–93.Google Scholar
  89. Jeltsch A. On the enzymatic properties of Dnmt1: specificity, processivity, mechanism of linear diffusion and allosteric regulation of the enzyme. Epigenetics. 2006;1(2):63–6.PubMedCrossRefGoogle Scholar
  90. Jeltsch A. Reading and writing DNA methylation. Nat Struct Mol Biol. 2008;15(10):1003–4.PubMedCrossRefGoogle Scholar
  91. Jeltsch A, Jurkowska RZ. Multimerization of the dnmt3a DNA methyltransferase and its functional implications. Prog Mol Biol Transl Sci. 2013;117:445–64.PubMedCrossRefGoogle Scholar
  92. Jeltsch A, Jurkowska RZ. New concepts in DNA methylation. Trends Biochem Sci. 2014;39(7):310–8.PubMedCrossRefGoogle Scholar
  93. Jeltsch A, Jurkowska RZ. Allosteric control of mammalian DNA Methyltransferases – a new regulatory paradigm. Nucl. Acids Res. 2016. doi: 10.1093/nar/gkw723.Google Scholar
  94. Jeong S, Liang GN, Sharma S, Lin JC, Choi SH, Han H, et al. Selective anchoring of DNA methyltransferases 3A and 3B to nucleosomes containing methylated DNA. Mol Cell Biol. 2009;29(19):5366–76.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Jia D, Jurkowska RZ, Zhang X, Jeltsch A, Cheng X. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature. 2007;449(7159):248–51.PubMedPubMedCentralCrossRefGoogle Scholar
  96. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13(7):484–92.PubMedCrossRefGoogle Scholar
  97. Jurkowska RZ, Anspach N, Urbanke C, Jia D, Reinhardt R, Nellen W, et al. Formation of nucleoprotein filaments by mammalian DNA methyltransferase Dnmt3a in complex with regulator Dnmt3L. Nucleic Acids Res. 2008;36(21):6656–63.PubMedPubMedCentralCrossRefGoogle Scholar
  98. Jurkowska RZ, Jurkowski TP, Jeltsch A. Structure and function of mammalian DNA methyltransferases. Chem Eur J Chem Biol. 2011a;12(2):206–22.CrossRefGoogle Scholar
  99. Jurkowska RZ, Rajavelu A, Anspach N, Urbanke C, Jankevicius G, Ragozin S, et al. Oligomerization and binding of the Dnmt3a DNA methyltransferase to parallel DNA molecules: heterochromatic localization and role of Dnmt3L. J Biol Chem. 2011b;286(27):24200–7.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Jurkowska RZ, Siddique AN, Jurkowski TP, Jeltsch A. Approaches to enzyme and substrate design of the murine Dnmt3a DNA methyltransferase. Chem Eur J Chem Biol. 2011c;12(10):1589–94.CrossRefGoogle Scholar
  101. Kareta MS, Botello ZM, Ennis JJ, Chou C, Chedin F. Reconstitution and mechanism of the stimulation of de novo methylation by human DNMT3L. J Biol Chem. 2006;281(36):25893–902.PubMedCrossRefGoogle Scholar
  102. Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, et al. Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell. 2006;23(4):607–18.PubMedCrossRefGoogle Scholar
  103. Kim SH, Park J, Choi MC, Kim HP, Park JH, Jung Y, et al. Zinc-fingers and homeoboxes 1 (ZHX1) binds DNA methyltransferase (DNMT) 3B to enhance DNMT3B-mediated transcriptional repression. Biochem Biophys Res Commun. 2007;355(2):318–23.PubMedCrossRefGoogle Scholar
  104. Kimura H, Shiota K. Methyl-CpG-binding protein, MeCP2, is a target molecule for maintenance DNA methyltransferase, Dnmt1. J Biol Chem. 2003;278(7):4806–12.PubMedCrossRefGoogle Scholar
  105. Klimasauskas S, Kumar S, Roberts RJ, Cheng X. HhaI methyltransferase flips its target base out of the DNA helix. Cell. 1994;76(2):357–69.PubMedCrossRefGoogle Scholar
  106. Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006;31(2):89–97.PubMedCrossRefGoogle Scholar
  107. Kolasinska-Zwierz P, Down T, Latorre I, Liu T, Liu XS, Ahringer J. Differential chromatin marking of introns and expressed exons by H3K36me3. Nat Genet. 2009;41(3):376–81.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Larschan E, Alekseyenko AA, Gortchakov AA, Peng S, Li B, Yang P, et al. MSL complex is attracted to genes marked by H3K36 trimethylation using a sequence-independent mechanism. Mol Cell. 2007;28(1):121–33.PubMedCrossRefGoogle Scholar
  109. Lavoie G, Esteve PO, Laulan NB, Pradhan S, St-Pierre Y. PKC isoforms interact with and phosphorylate DNMT1. BMC Biol. 2011;9:31.PubMedPubMedCentralCrossRefGoogle Scholar
  110. Leonhardt H, Page AW, Weier HU, Bestor TH. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell. 1992;71(5):865–73.PubMedCrossRefGoogle Scholar
  111. Li H, Rauch T, Chen ZX, Szabo PE, Riggs AD, Pfeifer GP. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J Biol Chem. 2006;281(28):19489–500.PubMedCrossRefGoogle Scholar
  112. Li JY, Pu MT, Hirasawa R, Li BZ, Huang YN, Zeng R, et al. Synergistic function of DNA methyltransferases Dnmt3a and Dnmt3b in the methylation of Oct4 and Nanog. Mol Cell Biol. 2007;27(24):8748–59.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Li BZ, Huang Z, Cui QY, Song XH, Du L, Jeltsch A, et al. Histone tails regulate DNA methylation by allosterically activating de novo methyltransferase. Cell Res. 2011;21(8):1172–81.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Lin IG, Han L, Taghva A, O’Brien LE, Hsieh CL. Murine de novo methyltransferase Dnmt3a demonstrates strand asymmetry and site preference in the methylation of DNA in vitro. Mol Cell Biol. 2002;22(3):704–23.PubMedPubMedCentralCrossRefGoogle Scholar
  115. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462(7271):315–22.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, et al. Global epigenomic reconfiguration during mammalian brain development. Science. 2013;341(6146):1237905.PubMedPubMedCentralCrossRefGoogle Scholar
  117. Liu Y, Oakeley EJ, Sun L, Jost JP. Multiple domains are involved in the targeting of the mouse DNA methyltransferase to the DNA replication foci. Nucleic Acids Res. 1998;26(4):1038–45.PubMedPubMedCentralCrossRefGoogle Scholar
  118. Liu X, Gao Q, Li P, Zhao Q, Zhang J, Li J, et al. UHRF1 targets DNMT1 for DNA methylation through cooperative binding of hemi-methylated DNA and methylated H3K9. Nat Commun. 2013;4:1563.PubMedCrossRefGoogle Scholar
  119. Lukashevich OV, Cherepanova NA, Jurkovska RZ, Jeltsch A, Gromova ES. Conserved motif VIII of murine DNA methyltransferase Dnmt3a is essential for methylation activity. BMC Biochem. 2016;17(1):7.PubMedPubMedCentralCrossRefGoogle Scholar
  120. Margot JB, Ehrenhofer-Murray AE, Leonhardt H. Interactions within the mammalian DNA methyltransferase family. BMC Mol Biol. 2003;4:7.PubMedPubMedCentralCrossRefGoogle Scholar
  121. Margueron R, Reinberg D. Chromatin structure and the inheritance of epigenetic information. Nat Rev Genet. 2010;11(4):285–96.PubMedPubMedCentralCrossRefGoogle Scholar
  122. Matzke MA, Mosher RA. RNA-directed DNA methylation: an epigenetic pathway of increasing complexity. Nat Rev Genet. 2014;15(6):394–408.PubMedCrossRefGoogle Scholar
  123. Meissner A, Mikkelsen TS, Gu H, Wernig M, Hanna J, Sivachenko A, et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature. 2008;454(7205):766–70.PubMedPubMedCentralGoogle Scholar
  124. Morselli M, Pastor WA, Montanini B, Nee K, Ferrari R, Fu K, et al. In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse. eLife. 2015;4:e06205.PubMedPubMedCentralCrossRefGoogle Scholar
  125. Muegge K. LSH, a guardian of heterochromatin at repeat elements. Biochem Cell Biol Biochimie et biologie cellulaire. 2005;83(4):548–54.Google Scholar
  126. Myant K, Stancheva I. LSH cooperates with DNA methyltransferases to repress transcription. Mol Cell Biol. 2008;28(1):215–26.PubMedCrossRefGoogle Scholar
  127. Nady N, Lemak A, Walker JR, Avvakumov GV, Kareta MS, Achour M, et al. Recognition of multivalent histone states associated with heterochromatin by UHRF1 protein. J Biol Chem. 2011;286(27):24300–11.PubMedPubMedCentralCrossRefGoogle Scholar
  128. Neri F, Krepelova A, Incarnato D, Maldotti M, Parlato C, Galvagni F, et al. Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs. Cell. 2013;155(1):121–34.PubMedCrossRefGoogle Scholar
  129. Nishiyama A, Yamaguchi L, Sharif J, Johmura Y, Kawamura T, Nakanishi K, et al. Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication. Nature. 2013;502(7470):249–53.PubMedCrossRefGoogle Scholar
  130. Noh KM, Wang H, Kim HR, Wenderski W, Fang F, Li CH, et al. Engineering of a histone-recognition domain in Dnmt3a alters the epigenetic landscape and phenotypic features of mouse ESCs. Mol Cell. 2015;59(1):89–103.PubMedPubMedCentralCrossRefGoogle Scholar
  131. O’Keefe RT, Henderson SC, Spector DL. Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences. J Cell Biol. 1992;116(5):1095–110.PubMedCrossRefGoogle Scholar
  132. Okano M, Xie SP, Li E. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet. 1998;19(3):219–20.PubMedCrossRefGoogle Scholar
  133. Ooi SK, Qiu C, Bernstein E, Li K, Jia D, Yang Z, et al. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature. 2007;448(7154):714–7.PubMedPubMedCentralCrossRefGoogle Scholar
  134. Osipiuk J, Walsh MA, Joachimiak A. Crystal structure of MboIIA methyltransferase. Nucleic Acids Res. 2003;31(18):5440–8.PubMedPubMedCentralCrossRefGoogle Scholar
  135. Otani J, Nankumo T, Arita K, Inamoto S, Ariyoshi M, Shirakawa M. Structural basis for recognition of H3K4 methylation status by the DNA methyltransferase 3A ATRX-DNMT3-DNMT3L domain. EMBO Rep. 2009;10(11):1235–41.PubMedPubMedCentralCrossRefGoogle Scholar
  136. Peng L, Yuan Z, Ling H, Fukasawa K, Robertson K, Olashaw N, et al. SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities. Mol Cell Biol. 2011;31(23):4720–34.PubMedPubMedCentralCrossRefGoogle Scholar
  137. Pradhan S, Esteve PO. Allosteric activator domain of maintenance human DNA (cytosine-5) methyltransferase and its role in methylation spreading. Biochemistry. 2003;42(18):5321–32.PubMedCrossRefGoogle Scholar
  138. Pradhan M, Esteve PO, Chin HG, Samaranayke M, Kim GD, Pradhan S. CXXC domain of human DNMT1 is essential for enzymatic activity. Biochemistry. 2008;47(38):10000–9.PubMedCrossRefGoogle Scholar
  139. Purdy MM, Holz-Schietinger C, Reich NO. Identification of a second DNA binding site in human DNA methyltransferase 3A by substrate inhibition and domain deletion. Arch Biochem Biophys. 2010;498(1):13–22.PubMedCrossRefGoogle Scholar
  140. Qin S, Min J. Structure and function of the nucleosome-binding PWWP domain. Trends Biochem Sci. 2014;39(11):536–47.PubMedCrossRefGoogle Scholar
  141. Qin W, Leonhardt H, Spada F. Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1. J Cell Biochem. 2011;112(2):439–44.PubMedCrossRefGoogle Scholar
  142. Qin W, Wolf P, Liu N, Link S, Smets M, La Mastra F, et al. DNA methylation requires a DNMT1 ubiquitin interacting motif (UIM) and histone ubiquitination. Cell Res. 2015;25(8):911–29.PubMedPubMedCentralCrossRefGoogle Scholar
  143. Qiu C, Sawada K, Zhang X, Cheng X. The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds. Nat Struct Biol. 2002;9(3):217–24.PubMedPubMedCentralGoogle Scholar
  144. Quenneville S, Verde G, Corsinotti A, Kapopoulou A, Jakobsson J, Offner S, et al. In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions. Mol Cell. 2011;44(3):361–72.PubMedPubMedCentralCrossRefGoogle Scholar
  145. Rajakumara E, Wang Z, Ma H, Hu L, Chen H, Lin Y, et al. PHD finger recognition of unmodified histone H3R2 links UHRF1 to regulation of euchromatic gene expression. Mol Cell. 2011;43(2):275–84.PubMedPubMedCentralCrossRefGoogle Scholar
  146. Rajavelu A, Jurkowska RZ, Fritz J, Jeltsch A. Function and disruption of DNA methyltransferase 3a cooperative DNA binding and nucleoprotein filament formation. Nucleic Acids Res. 2012;40(2):569–80.PubMedCrossRefGoogle Scholar
  147. Ramsahoye BH, Biniszkiewicz D, Lyko F, Clark V, Bird AP, Jaenisch R. Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc Natl Acad Sci U S A. 2000;97(10):5237–42.PubMedPubMedCentralCrossRefGoogle Scholar
  148. Reither S, Li F, Gowher H, Jeltsch A. Catalytic mechanism of DNA-(cytosine-C5)-methyltransferases revisited: covalent intermediate formation is not essential for methyl group transfer by the murine Dnmt3a enzyme. J Mol Biol. 2003;329(4):675–84.PubMedCrossRefGoogle Scholar
  149. Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66.PubMedCrossRefGoogle Scholar
  150. Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, et al. The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors. Nucleic Acids Res. 1999;27(11):2291–8.PubMedPubMedCentralCrossRefGoogle Scholar
  151. Rondelet G, Dal Maso T, Willems L, Wouters J. Structural basis for recognition of histone H3K36me3 nucleosome by human de novo DNA methyltransferases 3A and 3B. J Struct Biol. 2016;194(3):357–67.PubMedCrossRefGoogle Scholar
  152. Rothbart SB, Krajewski K, Nady N, Tempel W, Xue S, Badeaux AI, et al. Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation. Nat Struct Mol Biol. 2012;19(11):1155–60.PubMedPubMedCentralCrossRefGoogle Scholar
  153. Rothbart SB, Dickson BM, Ong MS, Krajewski K, Houliston S, Kireev DB, et al. Multivalent histone engagement by the linked tandem Tudor and PHD domains of UHRF1 is required for the epigenetic inheritance of DNA methylation. Genes Dev. 2013;27(11):1288–98.PubMedPubMedCentralCrossRefGoogle Scholar
  154. Scavetta RD, Thomas CB, Walsh MA, Szegedi S, Joachimiak A, Gumport RI, et al. Structure of RsrI methyltransferase, a member of the N6-adenine beta class of DNA methyltransferases. Nucleic Acids Res. 2000;28(20):3950–61.PubMedPubMedCentralCrossRefGoogle Scholar
  155. Schmitz KM, Mayer C, Postepska A, Grummt I. Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes. Genes Dev. 2010;24(20):2264–9.PubMedPubMedCentralCrossRefGoogle Scholar
  156. Schultz MD, He Y, Whitaker JW, Hariharan M, Mukamel EA, Leung D, et al. Human body epigenome maps reveal noncanonical DNA methylation variation. Nature. 2015;523(7559):212–6.PubMedPubMedCentralCrossRefGoogle Scholar
  157. Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo TA, et al. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature. 2007;450(7171):908–12.PubMedCrossRefGoogle Scholar
  158. Sharma S, De Carvalho DD, Jeong S, Jones PA, Liang G. Nucleosomes containing methylated DNA stabilize DNA methyltransferases 3A/3B and ensure faithful epigenetic inheritance. PLoS Genet. 2011;7(2):e1001286.PubMedPubMedCentralCrossRefGoogle Scholar
  159. Smallwood SA, Tomizawa S, Krueger F, Ruf N, Carli N, Segonds-Pichon A, et al. Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat Genet. 2011;43(8):811–4.PubMedPubMedCentralCrossRefGoogle Scholar
  160. Song J, Rechkoblit O, Bestor TH, Patel DJ. Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation. Science. 2011;331(6020):1036–40.PubMedCrossRefGoogle Scholar
  161. Song J, Teplova M, Ishibe-Murakami S, Patel DJ. Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation. Science. 2012;335(6069):709–12.PubMedPubMedCentralCrossRefGoogle Scholar
  162. Suetake I, Shinozaki F, Miyagawa J, Takeshima H, Tajima S. DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. J Biol Chem. 2004;279(26):27816–23.PubMedCrossRefGoogle Scholar
  163. Suetake I, Hayata D, Tajima S. The amino-terminus of mouse DNA methyltransferase 1 forms an independent domain and binds to DNA with the sequence involving PCNA binding motif. J Biochem. 2006;140(6):763–76.PubMedCrossRefGoogle Scholar
  164. Suetake I, Mishima Y, Kimura H, Lee YH, Goto Y, Takeshima H, et al. Characterization of DNA-binding activity in the N-terminal domain of the DNA methyltransferase Dnmt3a. Biochem J. 2011;437(1):141–8.PubMedCrossRefGoogle Scholar
  165. Sugiyama Y, Hatano N, Sueyoshi N, Suetake I, Tajima S, Kinoshita E, et al. The DNA-binding activity of mouse DNA methyltransferase 1 is regulated by phosphorylation with casein kinase 1delta/epsilon. Biochem J. 2010;427(3):489–97.PubMedCrossRefGoogle Scholar
  166. Suva ML, Riggi N, Bernstein BE. Epigenetic reprogramming in cancer. Science. 2013;339(6127):1567–70.PubMedCrossRefGoogle Scholar
  167. Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet. 2008;9(6):465–76.PubMedCrossRefGoogle Scholar
  168. Suzuki M, Yamada T, Kihara-Negishi F, Sakurai T, Hara E, Tenen DG, et al. Site-specific DNA methylation by a complex of PU.1 and Dnmt3a/b. Oncogene. 2006;25(17):2477–88.PubMedCrossRefGoogle Scholar
  169. Svedruzic ZM, Reich NO. DNA cytosine C5 methyltransferase Dnmt1: catalysis-dependent release of allosteric inhibition. Biochemistry. 2005;44(27):9472–85.PubMedCrossRefGoogle Scholar
  170. Syeda F, Fagan RL, Wean M, Avvakumov GV, Walker JR, Xue S, et al. The replication focus targeting sequence (RFTS) domain is a DNA-competitive inhibitor of Dnmt1. J Biol Chem. 2011;286(17):15344–51.PubMedPubMedCentralCrossRefGoogle Scholar
  171. Takeshima H, Suetake I, Tajima S. Mouse Dnmt3a preferentially methylates linker DNA and is inhibited by histone H1. J Mol Biol. 2008;383(4):810–21.PubMedCrossRefGoogle Scholar
  172. Takeshita K, Suetake I, Yamashita E, Suga M, Narita H, Nakagawa A, et al. Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1). Proc Natl Acad Sci U S A. 2011;108(22):9055–9.PubMedPubMedCentralCrossRefGoogle Scholar
  173. Vakoc CR, Sachdeva MM, Wang H, Blobel GA. Profile of histone lysine methylation across transcribed mammalian chromatin. Mol Cell Biol. 2006;26(24):9185–95.PubMedPubMedCentralCrossRefGoogle Scholar
  174. van Nuland R, van Schaik FM, Simonis M, van Heesch S, Cuppen E, Boelens R, et al. Nucleosomal DNA binding drives the recognition of H3K36-methylated nucleosomes by the PSIP1-PWWP domain. Epigenetics Chromatin. 2013;6(1):12.PubMedPubMedCentralCrossRefGoogle Scholar
  175. Varley KE, Gertz J, Bowling KM, Parker SL, Reddy TE, Pauli-Behn F, et al. Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res. 2013;23(3):555–67.PubMedPubMedCentralCrossRefGoogle Scholar
  176. Vilkaitis G, Suetake I, Klimasauskas S, Tajima S. Processive methylation of hemimethylated CpG sites by mouse Dnmt1 DNA methyltransferase. J Biol Chem. 2005;280(1):64–72.PubMedCrossRefGoogle Scholar
  177. Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006;439(7078):871–4.PubMedCrossRefGoogle Scholar
  178. Wang J, Hevi S, Kurash JK, Lei H, Gay F, Bajko J, et al. The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat Genet. 2009;41(1):125–9.PubMedCrossRefGoogle Scholar
  179. Wang C, Shen J, Yang Z, Chen P, Zhao B, Hu W, et al. Structural basis for site-specific reading of unmodified R2 of histone H3 tail by UHRF1 PHD finger. Cell Res. 2011;21(9):1379–82.PubMedPubMedCentralCrossRefGoogle Scholar
  180. Weber M, Hellmann I, Stadler MB, Ramos L, Paabo S, Rebhan M, et al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet. 2007;39(4):457–66.PubMedCrossRefGoogle Scholar
  181. Zhang Y, Rohde C, Tierling S, Jurkowski TP, Bock C, Santacruz D, et al. DNA methylation analysis of chromosome 21 gene promoters at single base pair and single allele resolution. PLoS Genet. 2009;5(3):e1000438.PubMedPubMedCentralCrossRefGoogle Scholar
  182. Zhang Y, Jurkowska R, Soeroes S, Rajavelu A, Dhayalan A, Bock I, et al. Chromatin methylation activity of Dnmt3a and Dnmt3a/3L is guided by interaction of the ADD domain with the histone H3 tail. Nucleic Acids Res. 2010;38(13):4246–53.PubMedPubMedCentralCrossRefGoogle Scholar
  183. Zhang G, Esteve PO, Chin HG, Terragni J, Dai N, Correa Jr IR, et al. Small RNA-mediated DNA (cytosine-5) methyltransferase 1 inhibition leads to aberrant DNA methylation. Nucleic Acids Res. 2015a;43(12):6112–24.PubMedPubMedCentralCrossRefGoogle Scholar
  184. Zhang ZM, Liu S, Lin K, Luo Y, Perry JJ, Wang Y, et al. Crystal structure of human DNA methyltransferase 1. J Mol Biol. 2015b;427(15):2520–31.PubMedPubMedCentralCrossRefGoogle Scholar
  185. Zhou Q, Agoston AT, Atadja P, Nelson WG, Davidson NE. Inhibition of histone deacetylases promotes ubiquitin-dependent proteasomal degradation of DNA methyltransferase 1 in human breast cancer cells. Mole Cancer Res MCR. 2008;6(5):873–83.CrossRefGoogle Scholar
  186. Zhu H, Geiman TM, Xi S, Jiang Q, Schmidtmann A, Chen T, et al. Lsh is involved in de novo methylation of DNA. EMBO J. 2006;25(2):335–45.PubMedPubMedCentralCrossRefGoogle Scholar
  187. Ziller MJ, Muller F, Liao J, Zhang Y, Gu H, Bock C, et al. Genomic distribution and inter-sample variation of non-CpG methylation across human cell types. PLoS Genet. 2011;7(12):e1002389.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.BioMed X Innovation CenterHeidelbergGermany
  2. 2.Institute of Biochemistry, Faculty of ChemistryUniversity of StuttgartStuttgartGermany

Personalised recommendations