5-methylcytosine DNA demethylation: More than losing a methyl group

Annual Review of Genetics

Volumn 46, Issue , 2012, Pages 419-441

  Franchini, Don Marc ^a   Schmitz, Kerstin Maike ^a   Petersen Mahrt, Svend K ^a  

^a FIRC INSTITUTE OF MOLECULAR ONCOLOGY   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

5 METHYLCYTOSINE; ACTIVATION INDUCED CYTIDINE DEAMINASE; DNA; DNA DEMETHYLASE; DNA GLYCOSYLTRANSFERASE; METHYL GROUP; METHYLTRANSFERASE; RNA; THYMINE; UNCLASSIFIED DRUG;

CHROMATIN; DEMETHYLATION; DNA DAMAGE; DNA MODIFICATION; DNA REPAIR; EXCISION REPAIR; GENOME; HUMAN; MISMATCH REPAIR; MUTATION; NONHUMAN; PRIORITY JOURNAL; REVIEW; RNA METABOLISM;

5-METHYLCYTOSINE; ANIMALS; CHROMATIN; CPG ISLANDS; DEAMINATION; DNA DAMAGE; DNA METHYLATION; DNA REPAIR; DNA-BINDING PROTEINS; EMBRYONIC STEM CELLS; EPIGENESIS, GENETIC; HISTONES; HUMANS; MAMMALS; MUTATION; PROTO-ONCOGENE PROTEINS; TRANSCRIPTION, GENETIC;

EID: 84870152439     PISSN: 00664197     EISSN: 15452948     Source Type: Book Series    
DOI: 10.1146/annurev-genet-110711-155451     Document Type: Review

References (149)

1. Acosta-Silva C, Branchadell V, Bertran J, Oliva A. 2010. Mutual relationship between stacking and hydrogen bonding in DNA. Theoretical study of guanine-cytosine, guanine-5-methylcytosine, and their dimers. J. Phys. Chem. B 114:10217-27
2. Almeida KH, Sobol RW. 2007. A unified view of base excision repair: lesion-dependent protein complexes regulated by post-translational modification. DNA Repair 6:695-711
3. Antequera F, Bird A. 1999. CpG islands as genomic footprints of promoters that are associated with replication origins. Curr. Biol. 9:R661-67
4. Aravind L, Koonin EV. 2001. TheDNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate- and iron-dependent dioxygenases. Genome Biol. 2:0007.1-0007.8
5. Arney KL, Bao S, Bannister AJ, Kouzarides T, Surani MA. 2002. Histonemethylation defines epigenetic asymmetry in the mouse zygote. Int. J. Dev. Biol. 46:317-20
6. Barnes DE, Lindahl T. 2004. Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu. Rev. Genet. 38:445-76
7. Barreto G, Schäfer A, Marhold J, Stach D, Swaminathan SK, et al. 2007. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature 445:671-75
8. Beale RC, Petersen-Mahrt SK, Watt IN, Harris RS, Rada C, Neuberger MS. 2004. Comparison of the differential context-dependence ofDNAdeamination by APOBEC enzymes: correlation withmutation spectra in vivo. J. Mol. Biol. 337:585-96
9. Belotserkovskaya R, Reinberg D. 2004. Facts aboutFACTand transcript elongation through chromatin. Curr. Opin. Genet. Dev. 14:139-46
10. Bernstein BE, Mikkelsen TS, Xie X, KamalM, Huebert DJ, et al. 2006. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:315-26
11. Bestor TH, Bourc'his D. 2004. Transposon silencing and imprint establishment in mammalian germ cells. Cold Spring Harb. Symp. Quant. Biol. 69:381-87
12. Bhutani N, Brady JJ, Damian M, Sacco A, Corbel SY, Blau HM. 2010. Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature 463:1042-47
13. Boland MJ, Christman JK. 2008. Characterization of Dnmt3b:thymine-DNA glycosylase interaction and stimulation of thymine glycosylase-mediated repair by DNAmethyltransferase(s) and RNA. J. Mol. Biol. 379:492-504
14. Bostick M, Kim JK, Estève P-O, Clark A, Pradhan S, Jacobsen SE. 2007. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 317:1760-64
15. Bransteitter R, Pham P, Scharff MD, Goodman MF. 2003. Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc. Natl. Acad. Sci. USA 100:4102-7
16. Bruniquel D, Schwartz RH. 2003. Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nat. Immunol. 4:235-40
17. Cedar H, Bergman Y. 2009. Linking DNA methylation and histone modification: patterns and paradigms. Nat. Rev. Genet. 10:295-304
18. Chandler SP, Guschin D, Landsberger N, Wolffe AP. 1999. The methyl-CpG binding transcriptional repressor MeCP2 stably associates with nucleosomal DNA. Biochemistry 38:7008-18
19. Chu G, Mayne L. 1996. Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy: Do the genes explain the diseases? Trends Genet. 12:187-92
20. Conticello SG, ThomasCJ, Petersen-Mahrt SK, Neuberger MS. 2005. Evolution of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases. Mol. Biol. Evol. 22:367-77
21. Cortazar D, Kunz C, Selfridge J, Lettieri T, Saito Y, et al. 2011. Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability. Nature 470:419-23
22. Cortellino S, Xu J, Sannai M, Moore R, Caretti E, et al. 2011. Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell 146:67-79
23. Cowell IG, Aucott R, Mahadevaiah SK, Burgoyne PS, Huskisson N, et al. 2002. Heterochromatin, HP1 and methylation at lysine 9 of histone H3 in animals. Chromosoma 111:22-36
24. Daujat S, Weiss T, Mohn F, Lange UC, Ziegler-Birling C, et al. 2009. H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming. Nat. Struct. Mol. Biol. 16:777-81
25. Di Noia JM, Neuberger MS. 2007. Molecular mechanisms of antibody somatic hypermutation. Annu. Rev. Biochem. 76:1-22
26. Erhardt S, Su IH, Schneider R, Barton S, Bannister AJ, et al. 2003. Consequences of the depletion of zygotic and embryonic enhancer of zeste 2 during preimplantation mouse development. Development 130:4235-48
27. Falnes POø, Klungland A, Alseth I. 2007. Repair of methyl lesions in DNA and RNA by oxidative demethylation. Neuroscience 145:1222-32
28. Felle M, Hoffmeister H, Rothammer J, Fuchs A, Exler JH, LängstG. 2011. Nucleosomes protectDNA from DNA methylation in vivo and in vitro. Nucleic Acids Res. 39:6956-69
29. Ficz G, Branco MR, Seisenberger S, Santos F, Krueger F, et al. 2011. Dynamic regulation of 5- hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 473:398-402
30. Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, et al. 2003. Induction of tumors in mice by genomic hypomethylation. Science 300:489-92
31. Gehring M, Reik W, Henikoff S. 2009. DNA demethylation by DNA repair. Trends Genet. 25:82-90
32. Goll MG, Bestor TH. 2005. Eukaryotic cytosine methyltransferases. Annu. Rev. Biochem. 74:481-514
33. Gribnau J, Hochedlinger K, Hata K, Li E, Jaenisch R. 2003. Asynchronous replication timing of imprinted loci is independent ofDNAmethylation, but consistent with differential subnuclear localization. Genes Dev. 17:759-73
34. Gu TP, Guo F, Yang H, Wu HP, Xu GF, et al. 2011. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477:606-10
35. Guo JU, Su Y, Zhong C, Ming GL, Song H. 2011. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145:423-34
36. Hajkova P, Ancelin K, Waldmann T, Lacoste N, Lange UC, et al. 2008. Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature 452:877-81
37. Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, et al. 2002. Epigenetic reprogramming in mouse primordial germ cells. Mech. Dev. 117:15-23
38. Hajkova P, Jeffries SJ, Lee C, Miller N, Jackson SP, Surani MA. 2010. Genome-wide reprogramming in the mouse germ line entails the base excision repair pathway. Science 329:78-82
39. Hardeland U, Bentele M, Jiricny J, Schär P. 2003. The versatile thymine DNA-glycosylase: a comparative characterization of the human, Drosophila and fission yeast orthologs. Nucleic Acids Res. 31:2261-71
40. Hardeland U, Steinacher R, Jiricny J, Schär P. 2002. Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover. EMBO J. 21:1456-64
41. Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, et al. 2003. DNA deamination mediates innate immunity to retroviral infection. Cell 113:803-9
42. Harris RS, Petersen-Mahrt SK, Neuberger MS. 2002. RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Mol. Cell 10:1247-53
43. He YF, Li BZ, Li Z, Liu P, Wang Y, et al. 2011. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333:1303-7
44. Hendrich B, Tweedie S. 2003. Themethyl-CpG binding domain and the evolving role ofDNA methylation in animals. Trends Genet. 19:269-77
45. Hervouet E, Lalier L, Debien E, Cheray M, Geairon A, et al. 2010. Disruption of Dnmt1/PCNA/ UHRF1 interactions promotes tumorigenesis from human and mice glial cells. PLoS ONE 5:e11333
46. Ikeda Y, Kinoshita T. 2009. DNA demethylation: a lesson from the garden. Chromosoma 18:37-41
47. Ikeda Y, Kinoshita Y, Susaki D, Ikeda Y, Iwano M, et al. 2011. HMG domain containing SSRP1 is required for DNA demethylation and genomic imprinting in Arabidopsis. Dev. Cell 21:589-96
48. IqbalK, Jin S-G, Pfeifer GP, Szabo PE. 2011. Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc. Natl. Acad. Sci. USA 108:3642-47
49. Ito S, D'Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y. 2010. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466:1129-33
50. Ito S, Shen L, Dai Q, Wu SC, Collins LB, et al. 2011. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333:1300-3
51. Jackson-Grusby L, Beard C, Possemato R, Tudor M, Fambrough D, et al. 2001. Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nat. Genet. 27:31-39
52. Jacobs AL, Schar P. 2012. DNA glycosylases: in DNA repair and beyond. Chromosoma 121:1-20
53. Jin S-G, Kadam S, Pfeifer GP. 2010. Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine. Nucleic Acids Res. 38:e125
54. Jin S-G, Wu X, Li AX, Pfeifer GP. 2011. Genomic mapping of 5-hydroxymethylcytosine in the human brain. Nucleic Acids Res. 39:5015-24
55. Jost JP. 1993. Nuclear extracts of chicken embryos promote an active demethylation ofDNAby excision repair of 5-methyldeoxycytidine. Proc. Natl. Acad. Sci. USA 90:4684-88
56. Kangaspeska S, Stride B, Metivier R, Polycarpou-Schwarz M, Ibberson D, et al. 2008. Transient cyclical methylation of promoter DNA. Nature 452:112-15
57. Kelsey G. 2011. DNA methylation: a new twist in the tail. Cell Res. 21:1155-56
58. Kersh EN, Fitzpatrick DR, Murali-Krishna K, Shires J, Speck SH, et al. 2006. Rapid demethylation of the IFN-γgene occurs in memory but not naive CD8 T cells. J. Immunol. 176:4083-93
59. Koh KP, Yabuuchi A, Rao S, Huang Y, Cunniff K, et al. 2011. Tet1 and Tet2 regulate 5- hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 8:200-13
60. Kriaucionis S, Heintz N. 2009. The nuclear DNA base 5- hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324:929-30
61. Lee J, Inoue K, Ono R, Ogonuki N, Kohda T, et al. 2002. Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells. Development 129:1807-17
62. Le May N, Mota-Fernandes D, Vélez-Cruz R, Iltis I, BiardD, Egly JM. 2010.NERfactors are recruited to active promoters and facilitate chromatin modification for transcription in the absence of exogenous genotoxic attack. Mol. Cell 38:54-66
63. Leteurtre F, Kohlhagen G, Fesen MR, Tanizawa A, Kohn KW, Pommier Y. 1994. Effects of DNA methylation on topoisomerase I and II cleavage activities. J. Biol. Chem. 269:7893-900
64. Lewis JD, Meehan RR, Henzel WJ, Maurer-Fogy I, Jeppesen P, et al. 1992. Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 69:905-14
65. Li BZ, Huang Z, Cui QY, Song XH, Du L, et al. 2011. Histone tails regulate DNA methylation by allosterically activating de novo methyltransferase. Cell Res. 21:1172-81
66. Li E, Bestor TH, Jaenisch R. 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915-26
67. Li YQ, Zhou PZ, Zheng XD, Walsh CP, Xu GL. 2007. Association of Dnmt3a and thymine DNA glycosylase links DNA methylation with base-excision repair. Nucleic Acids Res. 35:390-400
68. Lindahl T. 1993. Instability and decay of the primary structure of DNA. Nature 362:709-15
69. Liu H, Kim JM, Aoki F. 2004. Regulation of histone H3 lysine 9 methylation in oocytes and early pre-implantation embryos. Development 131:2269-80
70. Liu M, Duke JL, Richter DJ, Vinuesa CG, Goodnow CC, et al. 2008. Two levels of protection for the B cell genome during somatic hypermutation. Nature 451:841-45
71. Luijsterburg MS, von Bornstaedt G, Gourdin AM, Politi AZ, Moné MJ, et al. 2010. Stochastic and reversible assembly of a multiprotein DNA repair complex ensures accurate target site recognition and efficient repair. J. Cell Biol. 189:445-63
72. Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, et al. 2009. Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323:1074-77
73. Maiti A, Drohat AC. 2011. Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5- carboxylcytosine: potential implications for active demethylation ofCpGsites. J. Biol. Chem. 286:35334- 38
74. Matarazzo MR, Boyle S, D'Esposito M, Bickmore WA. 2007. Chromosome territory reorganization in a human disease with altered DNA methylation. Proc. Natl. Acad. Sci. USA 104:16546-51
75. Mayer W, Niveleau A, Walter J, Fundele R, Haaf T. 2000. Demethylation of the zygotic paternal genome. Nature 403:501-2
76. Meehan RR, Lewis JD, McKay S, Kleiner EL, Bird AP. 1989. Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs. Cell 58:499-507
77. Menoni H, Gasparutto D, Hamiche A, Cadet J, Dimitrov S, et al. 2007. ATP-dependent chromatin remodeling is required for base excision repair in conventional but not in variantH2A.Bbd nucleosomes. Mol. Cell Biol. 27:5949-56
78. Métivier R, Gallais R, Tiffoche C, Le Péron C, Jurkowska RZ, et al. 2008. Cyclical DNA methylation of a transcriptionally active promoter. Nature 452:45-50
79. Millar CB, Guy J, Sansom OJ, Selfridge J, MacDougall E, et al. 2002. Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice. Science 297:403-5
80. Mochizuki K, Matsui Y. 2010. Epigenetic profiles in primordial germ cells: global modulation and fine tuning of the epigenome for acquisition of totipotency. Dev. Growth Differ. 52:517-25
81. Modrich P. 2006. Mechanisms in eukaryotic mismatch repair. J. Biol. Chem. 281:30305-9
82. Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK. 2004. Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming. J. Biol. Chem. 279:52353-60
83. Nabel CS, Jia H, Ye Y, Shen L, Goldschmidt HL, et al. 2012. AID/APOBEC deaminases disfavor modified cytosines implicated in DNA demethylation. Nat. Chem. Biol. 8:751-58
84. Nabel CS, Manning SA, Kohli RM. 2012. The curious chemical biology of cytosine: deamination, methylation, and oxidation as modulators of genomic potential. ACS Chem. Biol. 7:20-30
85. Naegeli H, Sugasawa K. 2011. The xeroderma pigmentosum pathway: decision tree analysis of DNA quality. DNA Repair 10:673-83
86. Nakamura T, Arai Y, Umehara H, Masuhara M, Kimura T, et al. 2007. PGC7/Stella protects against DNA demethylation in early embryogenesis. Nat. Cell Biol. 9:64-71
87. Nakanishi S, Prasad R, Wilson SH, Smerdon M. 2007. Different structural states in oligonucleosomes are required for early versus late steps of base excision repair. Nucleic Acids Res. 35:4313-21
88. Northrop JK, Thomas RM, Wells AD, Shen H. 2006. Epigenetic remodeling of the IL-2 and IFN-γ loci in memory CD8 T cells is influenced by CD4 T cells. J. Immunol. 177:1062-69
89. Nyce J, Liu L, Jones PA. 1986. Variable effects of DNA-synthesis inhibitors upon DNA methylation in mammalian cells. Nucleic Acids Res. 14:4353-67
90. Okada Y, Yamagata K, Hong K, Wakayama T, Zhang Y. 2010. A role for the elongator complex in zygotic paternal genome demethylation. Nature 463:554-58
91. Okano M, Bell DW, Haber DA, Li E. 1999.DNAmethyltransferasesDnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247-57
92. Ooi SK, Qiu C, Bernstein E, Li K, Jia D, et al. 2007. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448:714-17
93. Pastor WA, Pape UJ, Huang Y, Henderson HR, Lister R, et al. 2011. Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature 473:394-97
94. Pauklin S, Sernandez IV, Bachmann G, Ramiro AR, Petersen-Mahrt SK. 2009. Estrogen directly activates AID transcription and function. J. Exp. Med. 206:99-111
95. Pavri R, Gazumyan A, Jankovic M, Di Virgilio M, Klein I, et al. 2010. Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. Cell 143:122- 33
96. Pena-Diaz J, Jiricny J. 2012. Mammalian mismatch repair: error-free or error-prone? Trends Biochem. Sci. 37:206-14
97. Penn NW, Suwalski R, O'Riley C, Bojanowski K, Yura R. 1972. The presence of 5- hydroxymethylcytosine in animal deoxyribonucleic acid. Biochem. J. 126:781-90
98. Petersen-Mahrt S. 2005. DNA deamination in immunity. Immunol. Rev. 203:80-97
99. Petersen-Mahrt SK, Harris RS, Neuberger MS. 2002. AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 418:99-103
100. Petersen-Mahrt SK, Neuberger MS. 2003. In vitro deamination of cytosine to uracil in single-stranded DNAby apolipoprotein B editing complex catalytic subunit 1 (APOBEC1). J. Biol. Chem. 278:19583-86
101. Popp C, Dean W, Feng S, Cokus SJ, Andrews S, et al. 2010. Genome-wide erasure ofDNAmethylation in mouse primordial germ cells is affected by AID deficiency. Nature 463:1101-5
102. Rai K, Huggins IJ, James SR, Karpf AR, Jones DA, Cairns BR. 2008. DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and Gadd45. Cell 135:1201-12
103. Rangam G, Schmitz K-M, Cobb AJA, Petersen-Mahrt SK. 2012. AID enzymatic activity is inversely proportional to the size of cytosine C5 orbital cloud. PloS ONE 7:e43279
104. Razin A, Szyf M, Kafri T, RollM, GilohH, et al. 1986. Replacement of 5-methylcytosine by cytosine: a possible mechanism for transient DNA demethylation during differentiation. Proc. Natl. Acad. Sci. USA 83:2827-31
105. Reik W, Dean W, Walter J. 2001. Epigenetic reprogramming in mammalian development. Science 293:1089-93
106. Rein T, Kobayashi T, Malott M, Leffak M, DePamphilis ML. 1999. DNA methylation at mammalian replication origins. J. Biol. Chem. 274:25792-800
107. Rich A, Nordheim A, Wang AH. 1984. The chemistry and biology of left-handed Z-DNA. Annu. Rev. Biochem. 53:791-846
108. Santos AP, Abranches R, Stoger E, Beven A, Viegas W, Shaw PJ. 2002. The architecture of interphase chromosomes and gene positioning are altered by changes inDNAmethylation and histone acetylation. J. Cell Sci. 115:4597-605
109. Santos F, Dean W. 2004. Epigenetic reprogramming during early development in mammals. Reproduction 127:643-51
110. Santos F, Peters AH, Otte AP, Reik W, Dean W. 2005. Dynamic chromatin modifications characterise the first cell cycle in mouse embryos. Dev. Biol. 280:225-36
111. Schäfer A, Schomacher L, Barreto G, Döderlein G, Niehrs C. 2010. Gemcitabine functions epigenetically by inhibiting repair mediated DNA demethylation. PLoS ONE 5:e14060
112. Schmitz K-M, Schmitt N, Hoffmann-Rohrer U, Schäfer A, Grummt I, Mayer C. 2009. TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation. Mol. Cell 33:344-53
113. Seki Y, Hayashi K, Itoh K, Mizugaki M, Saitou M, Matsui Y. 2005. Extensive and orderly reprogramming of genome-wide chromatin modifications associated with specification and early development of germ cells in mice. Dev. Biol. 278:440-58
114. Seki Y, Yamaji M, Yabuta Y, Sano M, Shigeta M, et al. 2007. Cellular dynamics associated with the genome-wide epigenetic reprogramming in migrating primordial germ cells in mice. Development 134:2627-38
115. Selth LA, Sigurdsson S, Svejstrup JQ. 2010. Transcript elongation by RNA polymerase II. Annu. Rev. Biochem. 79:271-93
116. Sharif J, MutoM, Takebayashi S-I, Suetake I, Iwamatsu A, et al. 2007. The SRA proteinNp95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature 450:908-12
117. Shen JC, Rideout WM3rd, Jones PA. 1994. The rate of hydrolytic deamination of 5-methylcytosine in double-stranded DNA. Nucleic Acids Res. 22:972-76
118. Sibghat-Ullah, Gallinari P, Xu YZ, Goodman MF, Bloom LB, et al. 1996. Base analog and neighboring base effects on substrate specificity of recombinant human G:T mismatch-specific thymine DNAglycosylase. Biochemistry 35:12926-32
119. Smith SS. 2000. Gilbert's conjecture: the search for DNA (cytosine-5) demethylases and the emergence of new functions for eukaryotic DNA (cytosine-5) methyltransferases. J. Mol. Biol. 32:1-7
120. Song CX, Szulwach KE, Fu Y, Dai Q, Yi C, et al. 2011. Selective chemical labeling reveals the genomewide distribution of 5-hydroxymethylcytosine. Nat. Biotechnol. 29:68-72
121. Song J, Rechkoblit O, Bestor TH, Patel DJ. 2011. Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation. Science 331:1036-40
122. Stanlie A, Aida M, Muramatsu M, Honjo T, Begum NA. 2010. Histone3 lysine4 trimethylation regulated by the facilitates chromatin transcription complex is critical for DNA cleavage in class switch recombination. Proc. Natl. Acad. Sci. USA 107:22190-95
123. Szwagierczak A, Bultmann S, Schmidt CS, Spada F, Leonhardt H. 2010. Sensitive enzymatic quantification of 5-hydroxymethylcytosine in genomic DNA. Nucleic Acids Res. 38:e181
124. Taberlay PC, Jones PA. 2011. DNA methylation and cancer. Prog. Drug Res. 67:1-23
125. TahilianiM, Koh KP, Shen Y, PastorWA, Bandukwala H, et al. 2009. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930-35
126. Tao Y, Xi S, Briones V, Muegge K. 2010. Lsh mediated RNA polymerase II stalling at HoxC6 and HoxC8 involves DNA methylation. PLoS ONE 5:e9163
127. Tate P, Bird A. 1993. Effects of DNA methylation on DNA-binding proteins and gene expression. Curr. Opin. Genet. Dev. 3:226-31
128. Thillainadesan G, Chitilian JM, Isovic M, Ablack JN, Mymryk JS, et al. 2012. TGF-β-dependent active demethylation and expression of the p15(ink4b) tumor suppressor are impaired by the ZNF217/CoREST complex. Mol. Cell 46:636-49
129. Thornburg LD, LaiMT, Wishnok JS, Stubbe J. 1993. A non-heme iron protein with heme tendencies: an investigation of the substrate specificity of thymine hydroxylase. Biochemistry 32:14023-33
130. Tini M, Benecke A, Um SJ, Torchia J, Evans RM, Chambon P. 2002. Association ofCBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription. Mol. Cell 9:265-77
131. Torres-Padilla ME, Bannister AJ, Hurd PJ, Kouzarides T, Zernicka-Goetz M. 2006. Dynamic distribution of the replacement histone variant H3.3 in the mouse oocyte and preimplantation embryos. Int. J. Dev. Biol. 50:455-61
132. Um S, Harbers M, Benecke A, Pierrat B, Losson R, Chambon P. 1998. Retinoic acid receptors interact physically and functionally with the T:G mismatch-specific thymine-DNA glycosylase. J. Biol. Chem. 273:20728-36
133. Valinluck V, Sowers LC. 2007. Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1. Cancer Res. 67:946-50
134. Valinluck V, Tsai H-H, RogstadDK, Burdzy A, Bird A, Sowers LC. 2004. Oxidative damage tomethyl- CpGsequences inhibits the binding of themethyl-CpG binding domain (MBD) ofmethyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res. 32:4100-8
135. van der Heijden GW, Dieker JW, Derijck AA, Muller S, Berden JH, et al. 2005. Asymmetry in histone H3 variants and lysinemethylation between paternal andmaternal chromatin of the early mouse zygote. Mech. Dev. 122:1008-22
136. Vardimon L, Kressmann A, Cedar H, Maechler M, Doerfler W.1982. Expression of a cloned adenovirus gene is inhibited by in vitro methylation. Proc. Natl. Acad. Sci. USA 79:1073-77
137. Watt F, Molloy PL. 1988. Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev. 2:1136-43
138. Williams K, Christensen J, Pedersen MT, Johansen JV, Cloos PA, et al. 2011. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 473:343-48
139. Willman KL, Milosevic S, Pauklin S, Schmitz K-M, Rangam G, et al. 2012. A role for the RNA pol II-associated PAF complex in AID-induced immune diversification. J. Exp. Med. In press
140. Wolffe AP, Jones PL, Wade PA. 1999. DNA demethylation. Proc. Natl. Acad. Sci. USA 96:5894-96
141. Wossidlo M, Arand J, Sebastiano V, Lepikhov K, Boiani M, et al. 2010. Dynamic link ofDNAdemethylation, DNA strand breaks and repair in mouse zygotes. EMBO J. 29:1877-88
142. Wu H, D'Alessio AC, Ito S, Xia K, Wang Z, et al. 2011. Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature 473:389-93
143. Wu SC, Zhang Y. 2010. Active DNA demethylation: Many roads lead to Rome. Nat. Rev. Mol. Cell Biol. 11:607-20
144. Wyatt GR, Cohen SS. 1952. A new pyrimidine base from bacteriophage nucleic acids. Nature 170:1072- 73
145. Xu Y, Wu F, Tan L, Kong L, Xiong L, et al. 2011. Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells. Mol. Cell 42:451-64
146. Zhu B, Zheng Y, Angliker H, Schwarz S, Thiry S, et al. 2000. 5-methylcytosine DNA glycosylase activity is also present in the human MBD4 (G/T mismatch glycosylase) and in a related avian sequence. Nucleic Acids Res. 28:4157-65
147. Zhu B, Zheng Y, Hess D, Angliker H, Schwarz S, et al. 2000. 5-methylcytosine-DNA glycosylase activity is present in a cloned G/T mismatch DNA glycosylase associated with the chicken embryo DNA demethylation complex. Proc. Natl. Acad. Sci. USA 97:5135-39
148. Zhu J-K. 2009. ActiveDNAdemethylationmediated byDNAglycosylases. Annu. Rev. Genet. 43:143-66
149. Zou X, Ma W, Solov'yov IA, Chipot C, Schulten K. 2011. Recognition of methylated DNA through methyl-CpG binding domain proteins. Nucleic Acids Res. 40:2747-58