Reversing DNA methylation: Mechanisms, genomics, and biological functions

Cell

Volumn 156, Issue 1-2, 2014, Pages 45-68

  Wu, Hao ^a,b   Zhang, Yi ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b HARVARD STEM CELL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOSINE; DIOXYGENASE; DNA GLYCOSYLTRANSFERASE; METHYL GROUP;

BIOLOGICAL FUNCTIONS; DEMETHYLATION; DNA METHYLATION; EXCISION REPAIR; GENOMICS; HUMAN; NONHUMAN; OXIDATION; PRIORITY JOURNAL; PROMOTER REGION; REVIEW; TRANSCRIPTION REGULATION;

5-METHYLCYTOSINE; ANIMALS; DNA METHYLATION; GENOME; HUMANS; OXIDOREDUCTASES, N-DEMETHYLATING; PROMOTER REGIONS, GENETIC;

EID: 84892763878     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2013.12.019     Document Type: Review

References (214)

1. G. Barreto, A. Schäfer, J. Marhold, D. Stach, S.K. Swaminathan, V. Handa, G. Döderlein, N. Maltry, W. Wu, F. Lyko, and C. Niehrs Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation Nature 445 2007 671 675
2. S.B. Baylin, and P.A. Jones A decade of exploring the cancer epigenome - biological and translational implications Nat. Rev. Cancer 11 2011 726 734
3. M.T. Bennett, M.T. Rodgers, A.S. Hebert, L.E. Ruslander, L. Eisele, and A.C. Drohat Specificity of human thymine DNA glycosylase depends on N-glycosidic bond stability J. Am. Chem. Soc. 128 2006 12510 12519
4. B.E. Bernstein, T.S. Mikkelsen, X. Xie, M. Kamal, D.J. Huebert, J. Cuff, B. Fry, A. Meissner, M. Wernig, and K. Plath et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells Cell 125 2006 315 326
5. N. Bhutani, J.J. Brady, M. Damian, A. Sacco, S.Y. Corbel, and H.M. Blau Reprogramming towards pluripotency requires AID-dependent DNA demethylation Nature 463 2010 1042 1047
6. A. Bird DNA methylation patterns and epigenetic memory Genes Dev. 16 2002 6 21
7. K. Blaschke, K.T. Ebata, M.M. Karimi, J.A. Zepeda-Martínez, P. Goyal, S. Mahapatra, A. Tam, D.J. Laird, M. Hirst, and A. Rao et al. Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells Nature 500 2013 222 226
8. M.J. Booth, M.R. Branco, G. Ficz, D. Oxley, F. Krueger, W. Reik, and S. Balasubramanian Quantitative sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution Science 336 2012 934 937
9. P. Borst, and R. Sabatini Base J: discovery, biosynthesis, and possible functions Annu. Rev. Microbiol. 62 2008 235 251
10. M. Bostick, J.K. Kim, P.O. Estève, A. Clark, S. Pradhan, and S.E. Jacobsen UHRF1 plays a role in maintaining DNA methylation in mammalian cells Science 317 2007 1760 1764
11. R. Bransteitter, P. Pham, M.D. Scharff, and M.F. Goodman Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase Proc. Natl. Acad. Sci. USA 100 2003 4102 4107
12. T. Chen, Y. Ueda, J.E. Dodge, Z. Wang, and E. Li Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b Mol. Cell. Biol. 23 2003 5594 5605
13. C.C. Chen, K.Y. Wang, and C.K. Shen The mammalian de novo DNA methyltransferases DNMT3A and DNMT3B are also DNA 5-hydroxymethylcytosine dehydroxymethylases J. Biol. Chem. 287 2012 33116 33121
14. J. Chen, L. Guo, L. Zhang, H. Wu, J. Yang, H. Liu, X. Wang, X. Hu, T. Gu, and Z. Zhou et al. Vitamin C modulates TET1 function during somatic cell reprogramming Nat. Genet. 45 2013 1504 1509
15. Q. Chen, Y. Chen, C. Bian, R. Fujiki, and X. Yu TET2 promotes histone O-GlcNAcylation during gene transcription Nature 493 2013 561 564
16. L. Cimmino, O. Abdel-Wahab, R.L. Levine, and I. Aifantis TET family proteins and their role in stem cell differentiation and transformation Cell Stem Cell 9 2011 193 204
17. S.J. Clark, J. Harrison, C.L. Paul, and M. Frommer High sensitivity mapping of methylated cytosines Nucleic Acids Res. 22 1994 2990 2997
18. T.A. Clark, X. Lu, K. Luong, Q. Dai, M. Boitano, S.W. Turner, C. He, and J. Korlach Enhanced 5-methylcytosine detection in single-molecule, real-time sequencing via Tet1 oxidation BMC Biol. 11 2013 4
19. B.M. Colquitt, W.E. Allen, G. Barnea, and S. Lomvardas Alteration of genic 5-hydroxymethylcytosine patterning in olfactory neurons correlates with changes in gene expression and cell identity Proc. Natl. Acad. Sci. USA 110 2013 14682 14687
20. S.G. Conticello The AID/APOBEC family of nucleic acid mutators Genome Biol. 9 2008 229
21. D. Cortázar, C. Kunz, J. Selfridge, T. Lettieri, Y. Saito, E. MacDougall, A. Wirz, D. Schuermann, A.L. Jacobs, and F. Siegrist et al. Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability Nature 470 2011 419 423
22. S. Cortellino, J. Xu, M. Sannai, R. Moore, E. Caretti, A. Cigliano, M. Le Coz, K. Devarajan, A. Wessels, and D. Soprano et al. Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair Cell 146 2011 67 79
23. Y. Costa, J. Ding, T.W. Theunissen, F. Faiola, T.A. Hore, P.V. Shliaha, M. Fidalgo, A. Saunders, M. Lawrence, and S. Dietmann et al. NANOG-dependent function of TET1 and TET2 in establishment of pluripotency Nature 495 2013 370 374
24. S.R. Dalton, and A. Bellacosa DNA demethylation by TDG Epigenomics 4 2012 459 467
25. L. Dang, D.W. White, S. Gross, B.D. Bennett, M.A. Bittinger, E.M. Driggers, V.R. Fantin, H.G. Jang, S. Jin, and M.C. Keenan et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate Nature 462 2009 739 744
26. M.M. Dawlaty, K. Ganz, B.E. Powell, Y.C. Hu, S. Markoulaki, A.W. Cheng, Q. Gao, J. Kim, S.W. Choi, D.C. Page, and R. Jaenisch Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development Cell Stem Cell 9 2011 166 175
27. M.M. Dawlaty, A. Breiling, T. Le, G. Raddatz, M.I. Barrasa, A.W. Cheng, Q. Gao, B.E. Powell, Z. Li, and M. Xu et al. Combined deficiency of Tet1 and Tet2 causes epigenetic abnormalities but is compatible with postnatal development Dev. Cell 24 2013 310 323
28. A.M. Deaton, and A. Bird CpG islands and the regulation of transcription Genes Dev. 25 2011 1010 1022
29. F. Delhommeau, S. Dupont, V. Della Valle, C. James, S. Trannoy, A. Massé, O. Kosmider, J.P. Le Couedic, F. Robert, and A. Alberdi et al. Mutation in TET2 in myeloid cancers N. Engl. J. Med. 360 2009 2289 2301
30. R. Deplus, B. Delatte, M.K. Schwinn, M. Defrance, J. Méndez, N. Murphy, M.A. Dawson, M. Volkmar, P. Putmans, and E. Calonne et al. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS EMBO J. 32 2013 645 655
31. C.A. Doege, K. Inoue, T. Yamashita, D.B. Rhee, S. Travis, R. Fujita, P. Guarnieri, G. Bhagat, W.B. Vanti, and A. Shih et al. Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2 Nature 488 2012 652 655
32. N. Engel, J.S. Tront, T. Erinle, N. Nguyen, K.E. Latham, C. Sapienza, B. Hoffman, and D.A. Liebermann Conserved DNA methylation in Gadd45a(-/-) mice Epigenetics 4 2009 98 99
33. M. Esteller Cancer epigenomics: DNA methylomes and histone-modification maps Nat. Rev. Genet. 8 2007 286 298
34. G. Fan, C. Beard, R.Z. Chen, G. Csankovszki, Y. Sun, M. Siniaia, D. Biniszkiewicz, B. Bates, P.P. Lee, and R. Kuhn et al. DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals J. Neurosci. 21 2001 788 797
35. G. Fan, K. Martinowich, M.H. Chin, F. He, S.D. Fouse, L. Hutnick, D. Hattori, W. Ge, Y. Shen, and H. Wu et al. DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling Development 132 2005 3345 3356
36. J. Feng, Y. Zhou, S.L. Campbell, T. Le, E. Li, J.D. Sweatt, A.J. Silva, and G. Fan Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons Nat. Neurosci. 13 2010 423 430
37. S. Feng, S.E. Jacobsen, and W. Reik Epigenetic reprogramming in plant and animal development Science 330 2010 622 627
38. G. Ficz, M.R. Branco, S. Seisenberger, F. Santos, F. Krueger, T.A. Hore, C.J. Marques, S. Andrews, and W. Reik Dynamic regulation of 5- hydroxymethylcytosine in mouse ES cells and during differentiation Nature 473 2011 398 402
39. G. Ficz, T.A. Hore, F. Santos, H.J. Lee, W. Dean, J. Arand, F. Krueger, D. Oxley, Y.L. Paul, and J. Walter et al. FGF signaling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency Cell Stem Cell 13 2013 351 359
40. M.E. Figueroa, O. Abdel-Wahab, C. Lu, P.S. Ward, J. Patel, A. Shih, Y. Li, N. Bhagwat, A. Vasanthakumar, and H.F. Fernandez et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation Cancer Cell 18 2010 553 567
41. Y.W. Fong, C. Cattoglio, and R. Tjian The intertwined roles of transcription and repair proteins Mol. Cell 52 2013 291 302
42. C. Frauer, T. Hoffmann, S. Bultmann, V. Casa, M.C. Cardoso, I. Antes, and H. Leonhardt Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain PLoS ONE 6 2011 e21306
43. J.M. Freudenberg, S. Ghosh, B.L. Lackford, S. Yellaboina, X. Zheng, R. Li, S. Cuddapah, P.A. Wade, G. Hu, and R. Jothi Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity Nucleic Acids Res. 40 2012 3364 3377
44. Y. Gao, J. Chen, K. Li, T. Wu, B. Huang, W. Liu, X. Kou, Y. Zhang, H. Huang, and Y. Jiang et al. Replacement of Oct4 by Tet1 during iPSC induction reveals an important role of DNA methylation and hydroxymethylation in reprogramming Cell Stem Cell 12 2013 453 469
45. D. Globisch, M. Münzel, M. Müller, S. Michalakis, M. Wagner, S. Koch, T. Brückl, M. Biel, and T. Carell Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates PLoS ONE 5 2010 e15367
46. M.G. Goll, and T.H. Bestor Eukaryotic cytosine methyltransferases Annu. Rev. Biochem. 74 2005 481 514
47. T.P. Gu, F. Guo, H. Yang, H.P. Wu, G.F. Xu, W. Liu, Z.G. Xie, L. Shi, X. He, and S.G. Jin et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes Nature 477 2011 606 610
48. J.U. Guo, Y. Su, C. Zhong, G.L. Ming, and H. Song Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain Cell 145 2011 423 434
49. E. Habibi, A.B. Brinkman, J. Arand, L.I. Kroeze, H.H. Kerstens, F. Matarese, K. Lepikhov, M. Gut, I. Brun-Heath, and N.C. Hubner et al. Whole-genome bisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells Cell Stem Cell 13 2013 360 369
50. J.A. Hackett, R. Sengupta, J.J. Zylicz, K. Murakami, C. Lee, T.A. Down, and M.A. Surani Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine Science 339 2013 448 452
51. M.A. Hahn, R. Qiu, X. Wu, A.X. Li, H. Zhang, J. Wang, J. Jui, S.G. Jin, Y. Jiang, G.P. Pfeifer, and Q. Lu Dynamics of 5-hydroxymethylcytosine and chromatin marks in Mammalian neurogenesis Cell Rep. 3 2013 291 300
52. P. Hajkova, S. Erhardt, N. Lane, T. Haaf, O. El-Maarri, W. Reik, J. Walter, and M.A. Surani Epigenetic reprogramming in mouse primordial germ cells Mech. Dev. 117 2002 15 23
53. P. Hajkova, S.J. Jeffries, C. Lee, N. Miller, S.P. Jackson, and M.A. Surani Genome-wide reprogramming in the mouse germ line entails the base excision repair pathway Science 329 2010 78 82
54. J.H. Hanna, K. Saha, and R. Jaenisch Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues Cell 143 2010 508 525
55. H. Hashimoto, P.M. Vertino, and X. Cheng Molecular coupling of DNA methylation and histone methylation Epigenomics 2 2010 657 669
56. H. Hashimoto, Y. Liu, A.K. Upadhyay, Y. Chang, S.B. Howerton, P.M. Vertino, X. Zhang, and X. Cheng Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation Nucleic Acids Res. 40 2012 4841 4849
57. H. Hashimoto, J.E. Pais, X. Zhang, L. Saleh, Z.-Q. Fu, N. Dai, I.R. Corrêa, Y. Zheng, and X. Cheng Structure of a Naegleria Tet-like dioxygenase in complex with 5-methylcytosine DNA Nature 2013 10.1038/nature12905 Published online December 25, 2013
58. Y.F. He, B.Z. Li, Z. Li, P. Liu, Y. Wang, Q. Tang, J. Ding, Y. Jia, Z. Chen, and L. Li et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA Science 333 2011 1303 1307
59. A. Hermann, R. Goyal, and A. Jeltsch The Dnmt1 DNA-(cytosine-C5)- methyltransferase methylates DNA processively with high preference for hemimethylated target sites J. Biol. Chem. 279 2004 48350 48359
60. R. Holliday, and J.E. Pugh DNA modification mechanisms and gene activity during development Science 187 1975 226 232
61. C.H. Hsu, K.L. Peng, M.L. Kang, Y.R. Chen, Y.C. Yang, C.H. Tsai, C.S. Chu, Y.M. Jeng, Y.T. Chen, and F.M. Lin et al. TET1 suppresses cancer invasion by activating the tissue inhibitors of metalloproteinases Cell Rep. 2 2012 568 579
62. L. Hu, Z. Li, J. Cheng, Q. Rao, W. Gong, M. Liu, Y.G. Shi, J. Zhu, P. Wang, and Y. Xu Crystal Structure of TET2-DNA Complex: Insight into TET-Mediated 5mC Oxidation Cell 155 2013 1545 1555
63. Y. Huang, W.A. Pastor, Y. Shen, M. Tahiliani, D.R. Liu, and A. Rao The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing PLoS ONE 5 2010 e8888
64. Y. Huang, W.A. Pastor, J.A. Zepeda-Martínez, and A. Rao The anti-CMS technique for genome-wide mapping of 5-hydroxymethylcytosine Nat. Protoc. 7 2012 1897 1908
65. A. Inoue, and Y. Zhang Replication-dependent loss of 5- hydroxymethylcytosine in mouse preimplantation embryos Science 334 2011 194
66. A. Inoue, L. Shen, Q. Dai, C. He, and Y. Zhang Generation and replication-dependent dilution of 5fC and 5caC during mouse preimplantation development Cell Res. 21 2011 1670 1676
67. K. Iqbal, S.G. Jin, G.P. Pfeifer, and P.E. Szabó Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine Proc. Natl. Acad. Sci. USA 108 2011 3642 3647
68. S. Ito, A.C. D'Alessio, O.V. Taranova, K. Hong, L.C. Sowers, and Y. Zhang Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification Nature 466 2010 1129 1133
69. S. Ito, L. Shen, Q. Dai, S.C. Wu, L.B. Collins, J.A. Swenberg, C. He, and Y. Zhang Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine Science 333 2011 1300 1303
70. M. Iurlaro, G. Ficz, D. Oxley, E.A. Raiber, M. Bachman, M.J. Booth, S. Andrews, S. Balasubramanian, and W. Reik A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation Genome Biol. 14 2013 R119
71. L.M. Iyer, M. Tahiliani, A. Rao, and L. Aravind Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids Cell Cycle 8 2009 1698 1710
72. R. Jaenisch, and A. Bird Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals Nat. Genet. 33 Suppl 2003 245 254
73. H. Ji, L.I. Ehrlich, J. Seita, P. Murakami, A. Doi, P. Lindau, H. Lee, M.J. Aryee, R.A. Irizarry, and K. Kim et al. Comprehensive methylome map of lineage commitment from haematopoietic progenitors Nature 467 2010 338 342
74. L. Jiang, J. Zhang, J.J. Wang, L. Wang, L. Zhang, G. Li, X. Yang, X. Ma, X. Sun, and J. Cai et al. Sperm, but not oocyte, DNA methylome is inherited by zebrafish early embryos Cell 153 2013 773 784
75. S.G. Jin, C. Guo, and G.P. Pfeifer GADD45A does not promote DNA demethylation PLoS Genet. 4 2008 e1000013
76. G.A. Kaas, C. Zhong, D.E. Eason, D.L. Ross, R.V. Vachhani, G.L. Ming, J.R. King, H. Song, and J.D. Sweatt TET1 controls CNS 5-methylcytosine hydroxylation, active DNA demethylation, gene transcription, and memory formation Neuron 79 2013 1086 1093
77. W.G. Kaelin Jr., and S.L. McKnight Influence of metabolism on epigenetics and disease Cell 153 2013 56 69
78. S. Kagiwada, K. Kurimoto, T. Hirota, M. Yamaji, and M. Saitou Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice EMBO J. 32 2013 340 353
79. M.W. Kellinger, C.X. Song, J. Chong, X.Y. Lu, C. He, and D. Wang 5-formylcytosine and 5-carboxylcytosine reduce the rate and substrate specificity of RNA polymerase II transcription Nat. Struct. Mol. Biol. 19 2012 831 833
80. K. Kemmerich, F.A. Dingler, C. Rada, and M.S. Neuberger Germline ablation of SMUG1 DNA glycosylase causes loss of 5-hydroxymethyluracil- and UNG-backup uracil-excision activities and increases cancer predisposition of Ung-/-Msh2-/- mice Nucleic Acids Res. 40 2012 6016 6025
81. R.J. Klose, E.M. Kallin, and Y. Zhang JmjC-domain-containing proteins and histone demethylation Nat. Rev. Genet. 7 2006 715 727
82. M. Ko, Y. Huang, A.M. Jankowska, U.J. Pape, M. Tahiliani, H.S. Bandukwala, J. An, E.D. Lamperti, K.P. Koh, and R. Ganetzky et al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2 Nature 468 2010 839 843
83. M. Ko, H.S. Bandukwala, J. An, E.D. Lamperti, E.C. Thompson, R. Hastie, A. Tsangaratou, K. Rajewsky, S.B. Koralov, and A. Rao Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice Proc. Natl. Acad. Sci. USA 108 2011 14566 14571
84. M. Ko, J. An, H.S. Bandukwala, L. Chavez, T. Aijö, W.A. Pastor, M.F. Segal, H. Li, K.P. Koh, and H. Lähdesmäki et al. Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX Nature 497 2013 122 126
85. H. Kobayashi, T. Sakurai, M. Imai, N. Takahashi, A. Fukuda, O. Yayoi, S. Sato, K. Nakabayashi, K. Hata, and Y. Sotomaru et al. Contribution of intragenic DNA methylation in mouse gametic DNA methylomes to establish oocyte-specific heritable marks PLoS Genet. 8 2012 e1002440
86. K.P. Koh, A. Yabuuchi, S. Rao, Y. Huang, K. Cunniff, J. Nardone, A. Laiho, M. Tahiliani, C.A. Sommer, and G. Mostoslavsky et al. Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells Cell Stem Cell 8 2011 200 213
87. R.M. Kohli, and Y. Zhang TET enzymes, TDG and the dynamics of DNA demethylation Nature 502 2013 472 479
88. S. Kriaucionis, and N. Heintz The nuclear DNA base 5- hydroxymethylcytosine is present in Purkinje neurons and the brain Science 324 2009 929 930
89. R. Kumar, L. DiMenna, N. Schrode, T.C. Liu, P. Franck, S. Muñoz-Descalzo, A.K. Hadjantonakis, A.A. Zarrin, J. Chaudhuri, O. Elemento, and T. Evans AID stabilizes stem-cell phenotype by removing epigenetic memory of pluripotency genes Nature 500 2013 89 92
90. N. Lane, W. Dean, S. Erhardt, P. Hajkova, A. Surani, J. Walter, and W. Reik Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse Genesis 35 2003 88 93
91. S.M. Langemeijer, R.P. Kuiper, M. Berends, R. Knops, M.G. Aslanyan, M. Massop, E. Stevens-Linders, P. van Hoogen, A.G. van Kessel, and R.A. Raymakers et al. Acquired mutations in TET2 are common in myelodysplastic syndromes Nat. Genet. 41 2009 838 842
92. Q. LaPlant, V. Vialou, H.E. Covington 3rd, D. Dumitriu, J. Feng, B.L. Warren, I. Maze, D.M. Dietz, E.L. Watts, and S.D. Iñiguez et al. Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens Nat. Neurosci. 13 2010 1137 1143
93. J.A. Law, and S.E. Jacobsen Establishing, maintaining and modifying DNA methylation patterns in plants and animals Nat. Rev. Genet. 11 2010 204 220
94. H.G. Leitch, K.R. McEwen, A. Turp, V. Encheva, T. Carroll, N. Grabole, W. Mansfield, B. Nashun, J.G. Knezovich, and A. Smith et al. Naive pluripotency is associated with global DNA hypomethylation Nat. Struct. Mol. Biol. 20 2013 311 316
95. X. Li, M. Ito, F. Zhou, N. Youngson, X. Zuo, P. Leder, and A.C. Ferguson-Smith A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints Dev. Cell 15 2008 547 557
96. Z. Li, X. Cai, C.L. Cai, J. Wang, W. Zhang, B.E. Petersen, F.C. Yang, and M. Xu Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies Blood 118 2011 4509 4518
97. W.W. Li, L. Gong, and H. Bayley Single-molecule detection of 5-hydroxymethylcytosine in DNA through chemical modification and nanopore analysis Angew. Chem. Int. Ed. Engl. 52 2013 4350 4355
98. C.G. Lian, Y. Xu, C. Ceol, F. Wu, A. Larson, K. Dresser, W. Xu, L. Tan, Y. Hu, and Q. Zhan et al. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma Cell 150 2012 1135 1146
99. R. Lister, M. Pelizzola, R.H. Dowen, R.D. Hawkins, G. Hon, J. Tonti-Filippini, J.R. Nery, L. Lee, Z. Ye, and Q.M. Ngo et al. Human DNA methylomes at base resolution show widespread epigenomic differences Nature 462 2009 315 322
100. R. Lister, E.A. Mukamel, J.R. Nery, M. Urich, C.A. Puddifoot, N.D. Johnson, J. Lucero, Y. Huang, A.J. Dwork, and M.D. Schultz et al. Global epigenomic reconfiguration during mammalian brain development Science 341 2013 1237905
101. Y. Liu, H. Toh, H. Sasaki, X. Zhang, and X. Cheng An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence Genes Dev. 26 2012 2374 2379
102. Z. Liutkeviciute, G. Lukinavicius, V. Masevicius, D. Daujotyte, and S. Klimasauskas Cytosine-5-methyltransferases add aldehydes to DNA Nat. Chem. Biol. 5 2009 400 402
103. C. Loenarz, and C.J. Schofield Physiological and biochemical aspects of hydroxylations and demethylations catalyzed by human 2-oxoglutarate oxygenases Trends Biochem. Sci. 36 2011 7 18
104. H.K. Long, N.P. Blackledge, and R.J. Klose ZF-CxxC domain-containing proteins, CpG islands and the chromatin connection Biochem. Soc. Trans. 41 2013 727 740
105. R.B. Lorsbach, J. Moore, S. Mathew, S.C. Raimondi, S.T. Mukatira, and J.R. Downing TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23) Leukemia 17 2003 637 641
106. X. Lu, C.X. Song, K. Szulwach, Z. Wang, P. Weidenbacher, P. Jin, and C. He Chemical modification-assisted bisulfite sequencing (CAB-Seq) for 5-carboxylcytosine detection in DNA J. Am. Chem. Soc. 135 2013 9315 9317
107. D.K. Ma, M.H. Jang, J.U. Guo, Y. Kitabatake, M.L. Chang, N. Pow-Anpongkul, R.A. Flavell, B. Lu, G.L. Ming, and H. Song Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis Science 323 2009 1074 1077
108. M.L. Maeder, J.F. Angstman, M.E. Richardson, S.J. Linder, V.M. Cascio, S.Q. Tsai, Q.H. Ho, J.D. Sander, D. Reyon, and B.E. Bernstein et al. Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins Nat. Biotechnol. 31 2013 1137 1142
109. A. Maiti, and A.C. Drohat Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites J. Biol. Chem. 286 2011 35334 35338
110. H. Marks, T. Kalkan, R. Menafra, S. Denissov, K. Jones, H. Hofemeister, J. Nichols, A. Kranz, A.F. Stewart, A. Smith, and H.G. Stunnenberg The transcriptional and epigenomic foundations of ground state pluripotency Cell 149 2012 590 604
111. F. Matarese, E. Carrillo-de Santa Pau, and H.G. Stunnenberg 5-Hydroxymethylcytosine: a new kid on the epigenetic block? Mol. Syst. Biol. 7 2011 562
112. W. Mayer, A. Niveleau, J. Walter, R. Fundele, and T. Haaf Demethylation of the zygotic paternal genome Nature 403 2000 501 502
113. M. Mellén, P. Ayata, S. Dewell, S. Kriaucionis, and N. Heintz MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system Cell 151 2012 1417 1430
114. D.M. Messerschmidt, W. de Vries, M. Ito, D. Solter, A. Ferguson-Smith, and B.B. Knowles Trim28 is required for epigenetic stability during mouse oocyte to embryo transition Science 335 2012 1499 1502
115. R. Métivier, R. Gallais, C. Tiffoche, C. Le Péron, R.Z. Jurkowska, R.P. Carmouche, D. Ibberson, P. Barath, F. Demay, and G. Reid et al. Cyclical DNA methylation of a transcriptionally active promoter Nature 452 2008 45 50
116. T.S. Mikkelsen, M. Ku, D.B. Jaffe, B. Issac, E. Lieberman, G. Giannoukos, P. Alvarez, W. Brockman, T.K. Kim, and R.P. Koche et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells Nature 448 2007 553 560
117. C.B. Millar, J. Guy, O.J. Sansom, J. Selfridge, E. MacDougall, B. Hendrich, P.D. Keightley, S.M. Bishop, A.R. Clarke, and A. Bird Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice Science 297 2002 403 405
118. E.A. Minor, B.L. Court, J.I. Young, and G. Wang Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine J. Biol. Chem. 288 2013 13669 13674
119. K. Moran-Crusio, L. Reavie, A. Shih, O. Abdel-Wahab, D. Ndiaye-Lobry, C. Lobry, M.E. Figueroa, A. Vasanthakumar, J. Patel, and X. Zhao et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation Cancer Cell 20 2011 11 24
120. H.D. Morgan, W. Dean, H.A. Coker, W. Reik, and S.K. Petersen-Mahrt Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming J. Biol. Chem. 279 2004 52353 52360
121. M. Münzel, D. Globisch, T. Brückl, M. Wagner, V. Welzmiller, S. Michalakis, M. Müller, M. Biel, and T. Carell Quantification of the sixth DNA base hydroxymethylcytosine in the brain Angew. Chem. Int. Ed. Engl. 49 2010 5375 5377
122. C.S. Nabel, H. Jia, Y. Ye, L. Shen, H.L. Goldschmidt, J.T. Stivers, Y. Zhang, and R.M. Kohli AID/APOBEC deaminases disfavor modified cytosines implicated in DNA demethylation Nat. Chem. Biol. 8 2012 751 758
123. T. Nakamura, Y. Arai, H. Umehara, M. Masuhara, T. Kimura, H. Taniguchi, T. Sekimoto, M. Ikawa, Y. Yoneda, and M. Okabe et al. PGC7/Stella protects against DNA demethylation in early embryogenesis Nat. Cell Biol. 9 2007 64 71
124. T. Nakamura, Y.J. Liu, H. Nakashima, H. Umehara, K. Inoue, S. Matoba, M. Tachibana, A. Ogura, Y. Shinkai, and T. Nakano PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos Nature 486 2012 415 419
125. S. Nguyen, K. Meletis, D. Fu, S. Jhaveri, and R. Jaenisch Ablation of de novo DNA methyltransferase Dnmt3a in the nervous system leads to neuromuscular defects and shortened lifespan Dev. Dyn. 236 2007 1663 1676
126. Y. Okada, K. Yamagata, K. Hong, T. Wakayama, and Y. Zhang A role for the elongator complex in zygotic paternal genome demethylation Nature 463 2010 554 558
127. M. Okano, S. Xie, and E. Li Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases Nat. Genet. 19 1998 219 220
128. M. Okano, D.W. Bell, D.A. Haber, and E. Li DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development Cell 99 1999 247 257
129. R. Ono, T. Taki, T. Taketani, M. Taniwaki, H. Kobayashi, and Y. Hayashi LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23) Cancer Res. 62 2002 4075 4080
130. S.K. Ooi, and T.H. Bestor The colorful history of active DNA demethylation Cell 133 2008 1145 1148
131. S.K. Ooi, C. Qiu, E. Bernstein, K. Li, D. Jia, Z. Yang, H. Erdjument-Bromage, P. Tempst, S.P. Lin, and C.D. Allis et al. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA Nature 448 2007 714 717
132. J. Oswald, S. Engemann, N. Lane, W. Mayer, A. Olek, R. Fundele, W. Dean, W. Reik, and J. Walter Active demethylation of the paternal genome in the mouse zygote Curr. Biol. 10 2000 475 478
133. J. Otani, K. Arita, T. Kato, M. Kinoshita, H. Kimura, I. Suetake, S. Tajima, M. Ariyoshi, and M. Shirakawa Structural basis of the versatile DNA recognition ability of the methyl-CpG binding domain of methyl-CpG binding domain protein 4 J. Biol. Chem. 288 2013 6351 6362
134. J. Otani, H. Kimura, J. Sharif, T.A. Endo, Y. Mishima, T. Kawakami, H. Koseki, M. Shirakawa, I. Suetake, and S. Tajima Cell cycle-dependent turnover of 5-hydroxymethyl Cytosine in mouse embryonic stem cells PLoS ONE 8 2013 e82961
135. W.A. Pastor, U.J. Pape, Y. Huang, H.R. Henderson, R. Lister, M. Ko, E.M. McLoughlin, Y. Brudno, S. Mahapatra, and P. Kapranov et al. Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells Nature 473 2011 394 397
136. W.A. Pastor, L. Aravind, and A. Rao TETonic shift: biological roles of TET proteins in DNA demethylation and transcription Nat. Rev. Mol. Cell Biol. 14 2013 341 356
137. B. Payer, M. Saitou, S.C. Barton, R. Thresher, J.P.C. Dixon, D. Zahn, W.H. Colledge, M.B.L. Carlton, T. Nakano, and M.A. Surani Stella is a maternal effect gene required for normal early development in mice Curr. Biol. 13 2003 2110 2117
138. T. Pfaffeneder, B. Hackner, M. Truss, M. Münzel, M. Müller, C.A. Deiml, C. Hagemeier, and T. Carell The discovery of 5-formylcytosine in embryonic stem cell DNA Angew. Chem. Int. Ed. Engl. 50 2011 7008 7012
139. F.M. Piccolo, H. Bagci, K.E. Brown, D. Landeira, J. Soza-Ried, A. Feytout, D. Mooijman, P. Hajkova, H.G. Leitch, and T. Tada et al. Different roles for Tet1 and Tet2 proteins in reprogramming-mediated erasure of imprints induced by EGC fusion Mol. Cell 49 2013 1023 1033
140. C. Popp, W. Dean, S. Feng, S.J. Cokus, S. Andrews, M. Pellegrini, S.E. Jacobsen, and W. Reik Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency Nature 463 2010 1101 1105
141. M.E. Potok, D.A. Nix, T.J. Parnell, and B.R. Cairns Reprogramming the maternal zebrafish genome after fertilization to match the paternal methylation pattern Cell 153 2013 759 772
142. S. Quenneville, G. Verde, A. Corsinotti, A. Kapopoulou, J. Jakobsson, S. Offner, I. Baglivo, P.V. Pedone, G. Grimaldi, A. Riccio, and D. Trono In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions Mol. Cell 44 2011 361 372
143. C. Quivoron, L. Couronné, V. Della Valle, C.K. Lopez, I. Plo, O. Wagner-Ballon, M. Do Cruzeiro, F. Delhommeau, B. Arnulf, and M.H. Stern et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis Cancer Cell 20 2011 25 38
144. K. Rai, I.J. Huggins, S.R. James, A.R. Karpf, D.A. Jones, and B.R. Cairns DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45 Cell 135 2008 1201 1212
145. E.A. Raiber, D. Beraldi, G. Ficz, H.E. Burgess, M.R. Branco, P. Murat, D. Oxley, M.J. Booth, W. Reik, and S. Balasubramanian Genome-wide distribution of 5-formylcytosine in embryonic stem cells is associated with transcription and depends on thymine DNA glycosylase Genome Biol. 13 2012 R69
146. A.D. Riggs X inactivation, differentiation, and DNA methylation Cytogenet. Cell Genet. 14 1975 9 25
147. A.B. Robertson, J.A. Dahl, C.B. Vågbø, P. Tripathi, H.E. Krokan, and A. Klungland A novel method for the efficient and selective identification of 5-hydroxymethylcytosine in genomic DNA Nucleic Acids Res. 39 2011 e55
148. A. Rudenko, M.M. Dawlaty, J. Seo, A.W. Cheng, J. Meng, T. Le, K.F. Faull, R. Jaenisch, and L.H. Tsai Tet1 is critical for neuronal activity-regulated gene expression and memory extinction Neuron 79 2013 1109 1122
149. M. Saitou, S. Kagiwada, and K. Kurimoto Epigenetic reprogramming in mouse pre-implantation development and primordial germ cells Development 139 2012 15 31
150. H. Sasaki, and Y. Matsui Epigenetic events in mammalian germ-cell development: reprogramming and beyond Nat. Rev. Genet. 9 2008 129 140
151. S. Schiesser, B. Hackner, T. Pfaffeneder, M. Müller, C. Hagemeier, M. Truss, and T. Carell Mechanism and stem-cell activity of 5-carboxycytosine decarboxylation determined by isotope tracing Angew. Chem. Int. Ed. Engl. 51 2012 6516 6520
152. K.M. Schmitz, N. Schmitt, U. Hoffmann-Rohrer, A. Schäfer, I. Grummt, and C. Mayer TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation Mol. Cell 33 2009 344 353
153. S. Seisenberger, S. Andrews, F. Krueger, J. Arand, J. Walter, F. Santos, C. Popp, B. Thienpont, W. Dean, and W. Reik The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells Mol. Cell 48 2012 849 862
154. S. Seisenberger, J.R. Peat, and W. Reik Conceptual links between DNA methylation reprogramming in the early embryo and primordial germ cells Curr. Opin. Cell Biol. 25 2013 281 288
155. J. Sharif, M. Muto, S. Takebayashi, I. Suetake, A. Iwamatsu, T.A. Endo, J. Shinga, Y. Mizutani-Koseki, T. Toyoda, and K. Okamura et al. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA Nature 450 2007 908 912
156. J.R. Shearstone, R. Pop, C. Bock, P. Boyle, A. Meissner, and M. Socolovsky Global DNA demethylation during mouse erythropoiesis in vivo Science 334 2011 799 802
157. Y. Shen, F. Yue, D.F. McCleary, Z. Ye, L. Edsall, S. Kuan, U. Wagner, J. Dixon, L. Lee, V.V. Lobanenkov, and B. Ren A map of the cis-regulatory sequences in the mouse genome Nature 488 2012 116 120
158. L. Shen, H. Wu, D. Diep, S. Yamaguchi, A.C. D'Alessio, H.L. Fung, K. Zhang, and Y. Zhang Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics Cell 153 2013 692 706
159. K. Shirane, H. Toh, H. Kobayashi, F. Miura, H. Chiba, T. Ito, T. Kono, and H. Sasaki Mouse oocyte methylomes at base resolution reveal genome-wide accumulation of non-CpG methylation and role of DNA methyltransferases PLoS Genet. 9 2013 e1003439
160. S.A. Smallwood, S. Tomizawa, F. Krueger, N. Ruf, N. Carli, A. Segonds-Pichon, S. Sato, K. Hata, S.R. Andrews, and G. Kelsey Dynamic CpG island methylation landscape in oocytes and preimplantation embryos Nat. Genet. 43 2011 811 814
161. J.A. Smiley, M. Kundracik, D.A. Landfried, V.R. Barnes Sr., and A.A. Axhemi Genes of the thymidine salvage pathway: thymine-7-hydroxylase from a Rhodotorula glutinis cDNA library and iso-orotate decarboxylase from Neurospora crassa Biochim. Biophys. Acta 1723 2005 256 264
162. Z.D. Smith, and A. Meissner DNA methylation: roles in mammalian development Nat. Rev. Genet. 14 2013 204 220
163. Z.D. Smith, M.M. Chan, T.S. Mikkelsen, H. Gu, A. Gnirke, A. Regev, and A. Meissner A unique regulatory phase of DNA methylation in the early mammalian embryo Nature 484 2012 339 344
164. C.X. Song, and C. He Potential functional roles of DNA demethylation intermediates Trends Biochem. Sci. 38 2013 480 484
165. C.X. Song, K.E. Szulwach, Y. Fu, Q. Dai, C. Yi, X. Li, Y. Li, C.H. Chen, W. Zhang, and X. Jian et al. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine Nat. Biotechnol. 29 2011 68 72
166. C.X. Song, T.A. Clark, X.Y. Lu, A. Kislyuk, Q. Dai, S.W. Turner, C. He, and J. Korlach Sensitive and specific single-molecule sequencing of 5-hydroxymethylcytosine Nat. Methods 9 2012 75 77
167. C.X. Song, C. Yi, and C. He Mapping recently identified nucleotide variants in the genome and transcriptome Nat. Biotechnol. 30 2012 1107 1116
168. C.-X. Song, K.E. Szulwach, Q. Dai, Y. Fu, S.-Q. Mao, L. Lin, C. Street, Y. Li, M. Poidevin, and H. Wu et al. Genome-wide profiling of 5-formylcytosine reveals its roles in epigenetic priming Cell 153 2013 678 691
169. S.J. Song, K. Ito, U. Ala, L. Kats, K. Webster, S.M. Sun, M. Jongen-Lavrencic, K. Manova-Todorova, J. Teruya-Feldstein, and D.E. Avigan et al. The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation Cell Stem Cell 13 2013 87 101
170. S.J. Song, L. Poliseno, M.S. Song, U. Ala, K. Webster, C. Ng, G. Beringer, N.J. Brikbak, X. Yuan, and L.C. Cantley et al. MicroRNA-antagonism regulates breast cancer stemness and metastasis via TET-family-dependent chromatin remodeling Cell 154 2013 311 324
171. C.G. Spruijt, F. Gnerlich, A.H. Smits, T. Pfaffeneder, P.W.T.C. Jansen, C. Bauer, M. Münzel, M. Wagner, M. Müller, and F. Khan et al. Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives Cell 152 2013 1146 1159
172. M.B. Stadler, R. Murr, L. Burger, R. Ivanek, F. Lienert, A. Schöler, E. van Nimwegen, C. Wirbelauer, E.J. Oakeley, and D. Gaidatzis et al. DNA-binding factors shape the mouse methylome at distal regulatory regions Nature 480 2011 490 495
173. J.T. Stivers, and Y.L. Jiang A mechanistic perspective on the chemistry of DNA repair glycosylases Chem. Rev. 103 2003 2729 2759
174. H. Stroud, S. Feng, S. Morey Kinney, S. Pradhan, and S.E. Jacobsen 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells Genome Biol. 12 2011 R54
175. K.E. Szulwach, X. Li, Y. Li, C.X. Song, J.W. Han, S. Kim, S. Namburi, K. Hermetz, J.J. Kim, and M.K. Rudd et al. Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells PLoS Genet. 7 2011 e1002154
176. K.E. Szulwach, X. Li, Y. Li, C.X. Song, H. Wu, Q. Dai, H. Irier, A.K. Upadhyay, M. Gearing, and A.I. Levey et al. 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging Nat. Neurosci. 14 2011 1607 1616
177. A. Szwagierczak, S. Bultmann, C.S. Schmidt, F. Spada, and H. Leonhardt Sensitive enzymatic quantification of 5-hydroxymethylcytosine in genomic DNA Nucleic Acids Res. 38 2010 e181
178. M. Tahiliani, K.P. Koh, Y. Shen, W.A. Pastor, H. Bandukwala, Y. Brudno, S. Agarwal, L.M. Iyer, D.R. Liu, L. Aravind, and A. Rao Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1 Science 324 2009 930 935
179. F. Tang, C. Barbacioru, E. Nordman, S. Bao, C. Lee, X. Wang, B.B. Tuch, E. Heard, K. Lao, and M.A. Surani Deterministic and stochastic allele specific gene expression in single mouse blastomeres PLoS ONE 6 2011 e21208
180. J.P. Thomson, J.M. Hunter, C.E. Nestor, D.S. Dunican, R. Terranova, J.G. Moggs, and R.R. Meehan Comparative analysis of affinity-based 5-hydroxymethylation enrichment techniques Nucleic Acids Res. 41 2013 e206
181. V. Valinluck, H.H. Tsai, D.K. Rogstad, A. Burdzy, A. Bird, and L.C. Sowers Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2) Nucleic Acids Res. 32 2004 4100 4108
182. P. Vella, A. Scelfo, S. Jammula, F. Chiacchiera, K. Williams, A. Cuomo, A. Roberto, J. Christensen, T. Bonaldi, K. Helin, and D. Pasini Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells Mol. Cell 49 2013 645 656
183. J.J. Vincent, Y. Huang, P.Y. Chen, S. Feng, J.H. Calvopiña, K. Nee, S.A. Lee, T. Le, A.J. Yoon, and K. Faull et al. Stage-specific roles for tet1 and tet2 in DNA demethylation in primordial germ cells Cell Stem Cell 12 2013 470 478
184. M. Wanunu, D. Cohen-Karni, R.R. Johnson, L. Fields, J. Benner, N. Peterman, Y. Zheng, M.L. Klein, and M. Drndic Discrimination of methylcytosine from hydroxymethylcytosine in DNA molecules J. Am. Chem. Soc. 133 2011 486 492
185. P.S. Ward, J. Patel, D.R. Wise, O. Abdel-Wahab, B.D. Bennett, H.A. Coller, J.R. Cross, V.R. Fantin, C.V. Hedvat, and A.E. Perl et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate Cancer Cell 17 2010 225 234
186. W.A. Whyte, S. Bilodeau, D.A. Orlando, H.A. Hoke, G.M. Frampton, C.T. Foster, S.M. Cowley, and R.A. Young Enhancer decommissioning by LSD1 during embryonic stem cell differentiation Nature 482 2012 221 225
187. K. Williams, J. Christensen, M.T. Pedersen, J.V. Johansen, P.A. Cloos, J. Rappsilber, and K. Helin TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity Nature 473 2011 343 348
188. M. Wossidlo, T. Nakamura, K. Lepikhov, C.J. Marques, V. Zakhartchenko, M. Boiani, J. Arand, T. Nakano, W. Reik, and J. Walter 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming Nat. Commun. 2 2011 241
189. S.C. Wu, and Y. Zhang Active DNA demethylation: many roads lead to Rome Nat. Rev. Mol. Cell Biol. 11 2010 607 620
190. H. Wu, and Y. Zhang Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation Genes Dev. 25 2011 2436 2452
191. H. Wu, and Y. Zhang Tet1 and 5-hydroxymethylation: a genome-wide view in mouse embryonic stem cells Cell Cycle 10 2011 2428 2436
192. H. Wu, V. Coskun, J. Tao, W. Xie, W. Ge, K. Yoshikawa, E. Li, Y. Zhang, and Y.E. Sun Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes Science 329 2010 444 448
193. H. Wu, A.C. D'Alessio, S. Ito, Z. Wang, K. Cui, K. Zhao, Y.E. Sun, and Y. Zhang Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells Genes Dev. 25 2011 679 684
194. H. Wu, A.C. D'Alessio, S. Ito, K. Xia, Z. Wang, K. Cui, K. Zhao, Y.E. Sun, and Y. Zhang Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells Nature 473 2011 389 393
195. M. Xiao, H. Yang, W. Xu, S. Ma, H. Lin, H. Zhu, L. Liu, Y. Liu, C. Yang, and Y. Xu et al. Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors Genes Dev. 26 2012 1326 1338
196. W. Xie, C.L. Barr, A. Kim, F. Yue, A.Y. Lee, J. Eubanks, E.L. Dempster, and B. Ren Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome Cell 148 2012 816 831
197. W. Xu, H. Yang, Y. Liu, Y. Yang, P. Wang, S.H. Kim, S. Ito, C. Yang, P. Wang, and M.T. Xiao et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases Cancer Cell 19 2011 17 30
198. Y. Xu, F. Wu, L. Tan, L. Kong, L. Xiong, J. Deng, A.J. Barbera, L. Zheng, H. Zhang, and S. Huang et al. Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells Mol. Cell 42 2011 451 464
199. Y. Xu, C. Xu, A. Kato, W. Tempel, J.G. Abreu, C. Bian, Y. Hu, D. Hu, B. Zhao, and T. Cerovina et al. Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development Cell 151 2012 1200 1213
200. S. Yamaguchi, K. Hong, R. Liu, L. Shen, A. Inoue, D. Diep, K. Zhang, and Y. Zhang Tet1 controls meiosis by regulating meiotic gene expression Nature 492 2012 443 447
201. S. Yamaguchi, L. Shen, Y. Liu, D. Sendler, and Y. Zhang Role of Tet1 in erasure of genomic imprinting Nature 504 2013 460 464
202. M. Yamaji, J. Ueda, K. Hayashi, H. Ohta, Y. Yabuta, K. Kurimoto, R. Nakato, Y. Yamada, K. Shirahige, and M. Saitou PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells Cell Stem Cell 12 2013 368 382
203. H. Yang, Y. Liu, F. Bai, J.Y. Zhang, S.H. Ma, J. Liu, Z.D. Xu, H.G. Zhu, Z.Q. Ling, and D. Ye et al. Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation Oncogene 32 2013 663 669
204. O. Yildirim, R. Li, J.H. Hung, P.B. Chen, X. Dong, L.S. Ee, Z. Weng, O.J. Rando, and T.G. Fazzio Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells Cell 147 2011 1498 1510
205. R. Yin, S.-Q. Mao, B. Zhao, Z. Chong, Y. Yang, C. Zhao, D. Zhang, H. Huang, J. Gao, and Z. Li et al. Ascorbic acid enhances Tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals J. Am. Chem. Soc. 135 2013 10396 10403
206. Q.L. Ying, J. Wray, J. Nichols, L. Batlle-Morera, B. Doble, J. Woodgett, P. Cohen, and A. Smith The ground state of embryonic stem cell self-renewal Nature 453 2008 519 523
207. M. Yu, G.C. Hon, K.E. Szulwach, C.X. Song, L. Zhang, A. Kim, X. Li, Q. Dai, Y. Shen, and B. Park et al. Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome Cell 149 2012 1368 1380
208. H. Zhang, X. Zhang, E. Clark, M. Mulcahey, S. Huang, and Y.G. Shi TET1 is a DNA-binding protein that modulates DNA methylation and gene transcription via hydroxylation of 5-methylcytosine Cell Res. 20 2010 1390 1393
209. L. Zhang, X. Lu, J. Lu, H. Liang, Q. Dai, G.L. Xu, C. Luo, H. Jiang, and C. He Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine- modified DNA Nat. Chem. Biol. 8 2012 328 330
210. R.R. Zhang, Q.Y. Cui, K. Murai, Y.C. Lim, Z.D. Smith, S. Jin, P. Ye, L. Rosa, Y.K. Lee, and H.P. Wu et al. Tet1 regulates adult hippocampal neurogenesis and cognition Cell Stem Cell 13 2013 237 245
211. J.K. Zhu Active DNA demethylation mediated by DNA glycosylases Annu. Rev. Genet. 43 2009 143 166
212. B. Zhu, Y. Zheng, D. Hess, H. Angliker, S. Schwarz, M. Siegmann, S. Thiry, and J.P. Jost 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 2000 5135 5139
213. D. Zilberman, D. Coleman-Derr, T. Ballinger, and S. Henikoff Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks Nature 456 2008 125 129
214. M.J. Ziller, H. Gu, F. Müller, J. Donaghey, L.T. Tsai, O. Kohlbacher, P.L. De Jager, E.D. Rosen, D.A. Bennett, and B.E. Bernstein et al. Charting a dynamic DNA methylation landscape of the human genome Nature 500 2013 477 481