Structure and Function of TET Enzymes

  • Xiaotong Yin
  • Yanhui XuEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 945)


Mammalian DNA methylation mainly occurs at the carbon-C5 position of cytosine (5mC). TET enzymes were discovered to successively oxidize 5mC to 5-hydromethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). TET enzymes and oxidized 5mC derivatives play important roles in various biological and pathological processes, including regulation of DNA demethylation, gene transcription, embryonic development, and oncogenesis. In this chapter, we will discuss the discovery of TET-mediated 5mC oxidation and the structure, function, and regulation of TET enzymes.


TET Epigenetic modification DNA demethylation 



















AlkB homolog 2


Activation-induced deaminase


Acute myeloid leukemia


Apolipoprotein B mRNA-editing enzyme complex


Base excision repair


Catalytic domain


Chromatin immunoprecipitation-sequencing


Chronic myelomonocytic leukemia






Cys-rich C-terminal


Cys-rich N-terminal


Cysteine rich


DNA 6mA demethylase


DNA methyltransferase


Double-stranded β-helix


Embryonic day 11.5


Fumarate hydratase


Host cell factor 1


Human embryonic kidney 293




Isocitrate dehydrogenase


Induced pluripotent stem cells


J-binding protein


Jumonji C


Liquid chromatography-mass spectrometry


Mouse embryonic fibroblasts


Mouse embryonic stem cells


Mesenchymal to epithelial


Nucleotide excision repair




O-linked β-N-acetylglucosamine transferase


Oct4, Sox2, Klf4, and c-Myc


Primordial germ cells

Pol II

RNA polymerase II




S-adenosyl methionine


Succinate dehydrogenase


Single-strand-selective monofunctional uracil DNA glycosylase 1




Tet-assisted bisulfite sequencing


Tricarboxylic acid


Thymine-DNA glycosylase


Ten-eleven translocation


Tet1, Sox2, Kf4, and c-Myc


Transcription start site





We thank Dr. Guoliang Xu and his lab members for critical reading of the manuscript. This work was supported by grants from the National Natural Science Foundation of China (31425008 and 91419301). We apologize that we could not cite many important papers due to space limitation.


  1. Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, Patel J, Wadleigh M, et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 2009;114(1):144–7. doi: 10.1182/blood-2009-03-210039.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Arioka Y, Watanabe A, Saito K, Yamada Y. Activation-induced cytidine deaminase alters the subcellular localization of Tet family proteins. PLoS One. 2012;7(9):e45031. doi: 10.1371/journal.pone.0045031.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16(1):6–21. doi: 10.1101/gad.947102.PubMedCrossRefGoogle Scholar
  4. Blaschke K, Ebata KT, Karimi MM, Zepeda-Martinez JA, Goyal P, Mahapatra S, et al. Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature. 2013;500(7461):222–6. doi: 10.1038/nature12362.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Branco MR, Ficz G, Reik W. Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nat Rev Genet. 2012;13(1):7–13. doi: 10.1038/nrg3080.Google Scholar
  6. Bruniquel D, Schwartz RH. Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nat Immunol. 2003;4(3):235–40. doi: 10.1038/ni887.PubMedCrossRefGoogle Scholar
  7. Chen CC, Wang KY, Shen CKJ. The Mammalian de Novo DNA methyltransferases DNMT3A and DNMT3B are also DNA 5-hydroxymethylcytosine dehydroxymethylases. J Biol Chem. 2012;287(40):33116–21. doi: 10.1074/Jbc.C112.406975.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Chen J, Guo L, Zhang L, Wu H, Yang J, Liu H, et al. Vitamin C modulates TET1 function during somatic cell reprogramming. Nat Genet. 2013a;45(12):1504–9. doi: 10.1038/ng.2807.PubMedCrossRefGoogle Scholar
  9. Chen Q, Chen Y, Bian C, Fujiki R, Yu X. TET2 promotes histone O-GlcNAcylation during gene transcription. Nature. 2013b;493(7433):561–4. doi: 10.1038/nature11742.PubMedCrossRefGoogle Scholar
  10. Cimmino L, Abdel-Wahab O, Levine RL, Aifantis I. TET family proteins and their role in stem cell differentiation and transformation. Cell Stem Cell. 2011;9(3):193–204. doi: 10.1016/J.Stem.2011.08.007.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Cliffe LJ, Kieft R, Southern T, Birkeland SR, Marshall M, Sweeney K, et al. JBP1 and JBP2 are two distinct thymidine hydroxylases involved in J biosynthesis in genomic DNA of African trypanosomes. Nucleic Acids Res. 2009;37(5):1452–62. doi: 10.1093/nar/gkn1067.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Cloos PA, Christensen J, Agger K, Maiolica A, Rappsilber J, Antal T, et al. The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3. Nature. 2006;442(7100):307–11. doi: 10.1038/nature04837.PubMedCrossRefGoogle Scholar
  13. Costa Y, Ding J, Theunissen TW, Faiola F, Hore TA, Shliaha PV, et al. NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature. 2013;495(7441):370–4. doi: 10.1038/nature11925.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Dawlaty MM, Ganz K, Powell BE, Hu YC, Markoulaki S, Cheng AW, et al. Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development. Cell Stem Cell. 2011;9(2):166–75. doi: 10.1016/J.Stem.2011.07.010.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Dawlaty MM, Breiling A, Le T, Raddatz G, Barrasa MI, Cheng AW, et al. Combined deficiency of Tet1 and Tet2 causes epigenetic abnormalities but is compatible with postnatal development. Dev Cell. 2013;24(3):310–23. doi: 10.1016/J.Devcel.2012.12.015.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Deplus R, Delatte B, Schwinn MK, Defrance M, Mendez J, Murphy N, et al. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J. 2013;32(5):645–55. doi: 10.1038/emboj.2012.357.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Doege CA, Inoue K, Yamashita T, Rhee DB, Travis S, Fujita R, et al. Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2. Nature. 2012;488(7413):652–5. doi: 10.1038/nature11333.PubMedCrossRefGoogle Scholar
  18. Englard S, Seifter S. The biochemical functions of ascorbic acid. Annu Rev Nutr. 1986;6:365–406. doi: 10.1146/ Scholar
  19. Esteban MA, Wang T, Qin B, Yang J, Qin D, Cai J, et al. Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell. 2010;6(1):71–9. doi: 10.1016/j.stem.2009.12.001.PubMedCrossRefGoogle Scholar
  20. Ficz G, Branco MR, Seisenberger S, Santos F, Krueger F, Hore TA, et al. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature. 2011;473(7347):398–402. doi: 10.1038/nature10008.PubMedCrossRefGoogle Scholar
  21. Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553–67. doi: 10.1016/j.ccr.2010.11.015.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Frauer C, Hoffmann T, Bultmann S, Casa V, Cardoso MC, Antes I, et al. Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain. PLoS One. 2011;6(6):e21306. doi: 10.1371/journal.pone.0021306.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Fu L, Guerrero CR, Zhong N, Amato NJ, Liu Y, Liu S, et al. Tet-mediated formation of 5-hydroxymethylcytosine in RNA. J Am Chem Soc. 2014;136(33):11582–5. doi: 10.1021/ja505305z.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Fu Y, Luo GZ, Chen K, Deng X, Yu M, Han D, et al. N6-methyldeoxyadenosine marks active transcription start sites in chlamydomonas. Cell. 2015;161(4):879–92. doi: 10.1016/j.cell.2015.04.010.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Gao Y, Chen J, Li K, Wu T, Huang B, Liu W, et al. Replacement of Oct4 by Tet1 during iPSC induction reveals an important role of DNA methylation and hydroxymethylation in reprogramming. Cell Stem Cell. 2013;12(4):453–69. doi: 10.1016/j.stem.2013.02.005.PubMedCrossRefGoogle Scholar
  26. Globisch D, Munzel M, Muller M, Michalakis S, Wagner M, Koch S, et al. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. PLoS One. 2010;5(12):e15367. doi: 10.1371/journal.pone.0015367.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Greer EL, Blanco MA, Gu L, Sendinc E, Liu J, Aristizabal-Corrales D, et al. DNA Methylation on N6-Adenine in C. elegans. Cell. 2015;161(4):868–78. doi: 10.1016/j.cell.2015.04.005.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Gu TP, Guo F, Yang H, Wu HP, Xu GF, Liu W, et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature. 2011;477(7366):606–10. doi: 10.1038/nature10443.PubMedCrossRefGoogle Scholar
  29. Guo JU, Su Y, Zhong C, Ming GL, Song H. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell. 2011;145(3):423–34. doi: 10.1016/j.cell.2011.03.022.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Guo F, Li X, Liang D, Li T, Zhu P, Guo H, et al. Active and passive demethylation of male and female pronuclear DNA in the mammalian zygote. Cell Stem Cell. 2014;15(4):447–58. doi: 10.1016/j.stem.2014.08.003.PubMedCrossRefGoogle Scholar
  31. Hackett JA, Sengupta R, Zylicz JJ, Murakami K, Lee C, Down TA, et al. Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine. Science. 2013;339(6118):448–52. doi: 10.1126/science.1229277.PubMedCrossRefGoogle Scholar
  32. Haffner MC, Chaux A, Meeker AK, Esopi DM, Gerber J, Pellakuru LG, et al. Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers. Oncotarget. 2011;2(8):627–37.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, et al. Epigenetic reprogramming in mouse primordial germ cells. Mech Dev. 2002;117(1–2):15–23.PubMedCrossRefGoogle Scholar
  34. Hamada S, Kim TD, Suzuki T, Itoh Y, Tsumoto H, Nakagawa H, et al. Synthesis and activity of N-oxalylglycine and its derivatives as Jumonji C-domain-containing histone lysine demethylase inhibitors. Bioorg Med Chem Lett. 2009;19(10):2852–5. doi: 10.1016/j.bmcl.2009.03.098.PubMedCrossRefGoogle Scholar
  35. Hanover JA, Krause MW, Love DC. Bittersweet memories: linking metabolism to epigenetics through O-GlcNAcylation. Nat Rev Mol Cell Biol. 2012;13(5):312–21. doi: 10.1038/nrm3334.PubMedCrossRefGoogle Scholar
  36. Hashimoto H, Liu Y, Upadhyay AK, Chang Y, Howerton SB, Vertino PM, et al. Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation. Nucleic Acids Res. 2012;40(11):4841–9. doi: 10.1093/nar/gks155.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Hashimoto H, Pais JE, Zhang X, Saleh L, Fu ZQ, Dai N, et al. Structure of a Naegleria Tet-like dioxygenase in complex with 5-methylcytosine DNA. Nature. 2014;506(7488):391–5. doi: 10.1038/nature12905.PubMedCrossRefGoogle Scholar
  38. He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science. 2011;333(6047):1303–7. doi: 10.1126/science.1210944.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Hemerly JP, Bastos AU, Cerutti JM. Identification of several novel non-p.R132 IDH1 variants in thyroid carcinomas. Eur J Endocrinol. 2010;163(5):747–55. doi: 10.1530/Eje-10-0473.PubMedCrossRefGoogle Scholar
  40. Hoffart LM, Barr EW, Guyer RB, Bollinger JM, Krebs C. Direct spectroscopic detection of a CH-cleaving high-spin Fe (IV) complex in a prolyl-4-hydroxylase. Proc Natl Acad Sci. 2006;103(40):14738–43.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Hoon DS, Spugnardi M, Kuo C, Huang SK, Morton DL, Taback B. Profiling epigenetic inactivation of tumor suppressor genes in tumors and plasma from cutaneous melanoma patients. Oncogene. 2004;23(22):4014–22. doi: 10.1038/sj.onc.1207505.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Hu L, Li Z, Cheng J, Rao Q, Gong W, Liu M, et al. Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation. Cell. 2013;155(7):1545–55. doi: 10.1016/j.cell.2013.11.020.PubMedCrossRefGoogle Scholar
  43. Hu X, Zhang L, Mao SQ, Li Z, Chen J, Zhang RR, et al. Tet and TDG mediate DNA demethylation essential for mesenchymal-to-epithelial transition in somatic cell reprogramming. Cell Stem Cell. 2014;14(4):512–22. doi: 10.1016/j.stem.2014.01.001.PubMedCrossRefGoogle Scholar
  44. Hu L, Lu J, Cheng J, Rao Q, Li Z, Hou H, et al. Structural insight into substrate preference for TET-mediated oxidation. Nature. 2015;527(7576):118–22. doi: 10.1038/nature15713.PubMedCrossRefGoogle Scholar
  45. Inoue A, Zhang Y. Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos. Science. 2011;334(6053):194. doi: 10.1126/science.1212483.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Inoue A, Shen L, Dai Q, He C, Zhang Y. Generation and replication-dependent dilution of 5fC and 5caC during mouse preimplantation development. Cell Res. 2011;21(12):1670–6. doi: 10.1038/cr.2011.189.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Iqbal K, Jin SG, Pfeifer GP, Szabo PE. Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc Natl Acad Sci U S A. 2011;108(9):3642–7. doi: 10.1073/Pnas.1014033108.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Ito S, D’Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature. 2010;466(7310):1129–33. doi: 10.1038/nature09303.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333(6047):1300–3. doi: 10.1126/Science.1210597.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Iyer LM, Tahiliani M, Rao A, Aravind L. Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids. Cell Cycle. 2009;8(11):1698–710.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Iyer LM, Zhang D, Burroughs AM, Aravind L. Computational identification of novel biochemical systems involved in oxidation, glycosylation and other complex modifications of bases in DNA. Nucleic Acids Res. 2013;41(16):7635–55. doi: 10.1093/nar/gkt573.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33(Suppl):245–54. doi: 10.1038/ng1089.PubMedCrossRefGoogle Scholar
  53. Kaas GA, Zhong C, Eason DE, Ross DL, Vachhani RV, Ming GL, et al. TET1 controls CNS 5-methylcytosine hydroxylation, active DNA demethylation, gene transcription, and memory formation. Neuron. 2013;79(6):1086–93. doi: 10.1016/j.neuron.2013.08.032.PubMedCrossRefGoogle Scholar
  54. Kangaspeska S, Stride B, Metivier R, Polycarpou-Schwarz M, Ibberson D, Carmouche RP, et al. Transient cyclical methylation of promoter DNA. Nature. 2008;452(7183):112–5. doi: 10.1038/nature06640.PubMedCrossRefGoogle Scholar
  55. Ko M, Huang Y, Jankowska AM, Pape UJ, Tahiliani M, Bandukwala HS, et al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature. 2010;468(7325):839–43. doi: 10.1038/nature09586.PubMedPubMedCentralCrossRefGoogle Scholar
  56. Ko M, An J, Bandukwala HS, Chavez L, Aijo T, Pastor WA, et al. Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX. Nature. 2013;497(7447):122–6. doi: 10.1038/nature12052.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Koh KP, Yabuuchi A, Rao S, Huang Y, Cunniff K, Nardone J, et al. Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell. 2011;8(2):200–13. doi: 10.1016/j.stem.2011.01.008.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Krebs C, Galonic Fujimori D, Walsh CT, Bollinger Jr JM. Non-heme Fe(IV)-oxo intermediates. Acc Chem Res. 2007;40(7):484–92. doi: 10.1021/ar700066p.PubMedCrossRefGoogle Scholar
  59. Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science. 2009;324(5929):929–30. doi: 10.1126/science.1169786.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Kurimoto K, Yabuta Y, Ohinata Y, Shigeta M, Yamanaka K, Saitou M. Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice. Genes Dev. 2008;22(12):1617–35. doi: 10.1101/gad.1649908.PubMedPubMedCentralCrossRefGoogle Scholar
  61. Langemeijer SM, Kuiper RP, Berends M, Knops R, Aslanyan MG, Massop M, et al. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet. 2009;41(7):838–42. doi: 10.1038/ng.391.PubMedCrossRefGoogle Scholar
  62. Lee J, Inoue K, Ono R, Ogonuki N, Kohda T, Kaneko-Ishino T, et al. Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells. Development. 2002;129(8):1807–17.PubMedGoogle Scholar
  63. Lian CG, Xu Y, Ceol C, Wu F, Larson A, Dresser K, et al. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell. 2012;150(6):1135–46. doi: 10.1016/j.cell.2012.07.033.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Liu CK, Hsu CA, Abbott MT. Catalysis of three sequential dioxygenase reactions by thymine 7-hydroxylase. Arch Biochem Biophys. 1973;159(1):180–7.PubMedCrossRefGoogle Scholar
  65. Liu S, Ren S, Howell P, Fodstad O, Riker AI. Identification of novel epigenetically modified genes in human melanoma via promoter methylation gene profiling. Pigment Cell Melanoma Res. 2008;21(5):545–58. doi: 10.1111/j.1755-148X.2008.00484.x.PubMedCrossRefGoogle Scholar
  66. Liutkeviciute Z, Lukinavicius G, Masevicius V, Daujotyte D, Klimasauskas S. Cytosine-5-methyltransferases add aldehydes to DNA. Nat Chem Biol. 2009;5(6):400–2. doi: 10.1038/nchembio.172.PubMedCrossRefGoogle Scholar
  67. Liutkeviciute Z, Kriukiene E, Licyte J, Rudyte M, Urbanaviciute G, Klimasauskas S. Direct decarboxylation of 5-carboxylcytosine by DNA C5-methyltransferases. J Am Chem Soc. 2014;136(16):5884–7. doi: 10.1021/ja5019223.PubMedCrossRefGoogle Scholar
  68. Loenarz C, Schofield CJ. Expanding chemical biology of 2-oxoglutarate oxygenases. Nat Chem Biol. 2008;4(3):152–6. doi: 10.1038/nchembio0308-152.PubMedCrossRefGoogle Scholar
  69. Long HK, Blackledge NP, Klose RJ. ZF-CxxC domain-containing proteins, CpG islands and the chromatin connection. Biochem Soc Trans. 2013;41(3):727–40. doi: 10.1042/BST20130028.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Lu X, Han D, Zhao BS, Song CX, Zhang LS, Dore LC, et al. Base-resolution maps of 5-formylcytosine and 5-carboxylcytosine reveal genome-wide DNA demethylation dynamics. Cell Res. 2015;25(3):386–9. doi: 10.1038/cr.2015.5.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Maiti A, Drohat AC. Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine potential implications for active demethylation of CpG sites. J Biol Chem. 2011;286(41):35334–8. doi: 10.1074/Jbc.C111.284620.PubMedPubMedCentralCrossRefGoogle Scholar
  72. Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med. 2009;361(11):1058–66. doi: 10.1056/Nejmoa0903840.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, et al. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science. 2003;302(5646):890–3. doi: 10.1126/science.1090842.PubMedCrossRefGoogle Scholar
  74. Mayer W, Niveleau A, Walter J, Fundele R, Haaf T. Embryogenesis - demethylation of the zygotic paternal genome. Nature. 2000;403(6769):501–2. doi: 10.1038/35000656.PubMedCrossRefGoogle Scholar
  75. McDonough MA, Loenarz C, Chowdhury R, Clifton IJ, Schofield CJ. Structural studies on human 2-oxoglutarate dependent oxygenases. Curr Opin Struct Biol. 2010;20(6):659–72. doi: 10.1016/ Scholar
  76. Mellen M, Ayata P, Dewell S, Kriaucionis S, Heintz N. MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell. 2012;151(7):1417–30. doi: 10.1016/j.cell.2012.11.022.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Metivier R, Gallais R, Tiffoche C, Le Peron C, Jurkowska RZ, Carmouche RP, et al. Cyclical DNA methylation of a transcriptionally active promoter. Nature. 2008;452(7183):45–50. doi: 10.1038/nature06544.PubMedCrossRefGoogle Scholar
  78. Minor EA, Court BL, Young JI, Wang G. Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine. J Biol Chem. 2013;288(19):13669–74. doi: 10.1074/jbc.C113.464800.PubMedPubMedCentralCrossRefGoogle Scholar
  79. Moran-Crusio K, Reavie L, Shih A, Abdel-Wahab O, Ndiaye-Lobry D, Lobry C, et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell. 2011;20(1):11–24. doi: 10.1016/j.ccr.2011.06.001.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Muller I, Stuckl C, Wakeley J, Kertesz M, Uson I. Succinate complex crystal structures of the alpha-ketoglutarate-dependent dioxygenase AtsK: steric aspects of enzyme self-hydroxylation. J Biol Chem. 2005;280(7):5716–23. doi: 10.1074/jbc.M410840200.PubMedCrossRefGoogle Scholar
  81. Munzel M, Globisch D, Bruckl T, Wagner M, Welzmiller V, Michalakis S, et al. Quantification of the sixth DNA base hydroxymethylcytosine in the brain. Angew Chem Int Ed Engl. 2010;49(31):5375–7. doi: 10.1002/anie.201002033.PubMedCrossRefGoogle Scholar
  82. Myllyla R, Kuutti-Savolainen ER, Kivirikko KI. The role of ascorbate in the prolyl hydroxylase reaction. Biochem Biophys Res Commun. 1978;83(2):441–8.PubMedCrossRefGoogle Scholar
  83. Nabel CS, Jia H, Ye Y, Shen L, Goldschmidt HL, Stivers JT, et al. AID/APOBEC deaminases disfavor modified cytosines implicated in DNA demethylation. Nat Chem Biol. 2012;8(9):751–8. doi: 10.1038/nchembio.1042.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Nakamura T, Arai Y, Umehara H, Masuhara M, Kimura T, Taniguchi H, et al. PGC7/Stella protects against DNA demethylation in early embryogenesis. Nat Cell Biol. 2007;9(1):64–71. doi: 10.1038/ncb1519.PubMedCrossRefGoogle Scholar
  85. Neidigh JW, Darwanto A, Williams AA, Wall NR, Sowers LC. Cloning and characterization of Rhodotorula glutinis thymine hydroxylase. Chem Res Toxicol. 2009;22(5):885–93. doi: 10.1021/tx8004482.PubMedCrossRefGoogle Scholar
  86. Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y. 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. 2002;62(14):4075–80.PubMedGoogle Scholar
  87. Oswald J, Engemann S, Lane N, Mayer W, Olek A, Fundele R, et al. Active demethylation of the paternal genome in the mouse zygote. Curr Biol. 2000;10(8):475–8.PubMedCrossRefGoogle Scholar
  88. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321(5897):1807–12. doi: 10.1126/science.1164382.PubMedPubMedCentralCrossRefGoogle Scholar
  89. Pastor WA, Aravind L, Rao A. TETonic shift: biological roles of TET proteins in DNA demethylation and transcription. Nat Rev Mol Cell Biol. 2013;14(6):341–56. doi: 10.1038/nrm3589.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Pfaffeneder T, Hackner B, Truss M, Munzel M, Muller M, Deiml CA, et al. The discovery of 5-formylcytosine in embryonic stem cell DNA. Angew Chem Int Ed Engl. 2011;50(31):7008–12. doi: 10.1002/anie.201103899.PubMedCrossRefGoogle Scholar
  91. Price JC, Barr EW, Glass TE, Krebs C, Bollinger Jr JM. Evidence for hydrogen abstraction from C1 of taurine by the high-spin Fe(IV) intermediate detected during oxygen activation by taurine:alpha-ketoglutarate dioxygenase (TauD). J Am Chem Soc. 2003;125(43):13008–9. doi: 10.1021/ja037400h.PubMedCrossRefGoogle Scholar
  92. Quivoron C, Couronne L, Della Valle V, Lopez CK, Plo I, Wagner-Ballon O, et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell. 2011;20(1):25–38. doi: 10.1016/j.ccr.2011.06.003.PubMedCrossRefGoogle Scholar
  93. Rampal R, Alkalin A, Madzo J, Vasanthakumar A, Pronier E, Patel J, et al. DNA hydroxymethylation profiling reveals that WT1 mutations result in loss of TET2 function in acute myeloid leukemia. Cell Rep. 2014;9(5):1841–55. doi: 10.1016/j.celrep.2014.11.004.PubMedPubMedCentralCrossRefGoogle Scholar
  94. Rangam G, Schmitz KM, Cobb AJ, Petersen-Mahrt SK. AID enzymatic activity is inversely proportional to the size of cytosine C5 orbital cloud. PLoS One. 2012;7(8):e43279. doi: 10.1371/journal.pone.0043279.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Rudenko A, Dawlaty MM, Seo J, Cheng AW, Meng J, Le T, et al. Tet1 is critical for neuronal activity-regulated gene expression and memory extinction. Neuron. 2013;79(6):1109–22. doi: 10.1016/J.Neuron.2013.08.003.PubMedPubMedCentralCrossRefGoogle Scholar
  96. Ruzov A, Tsenkina Y, Serio A, Dudnakova T, Fletcher J, Bai Y, et al. Lineage-specific distribution of high levels of genomic 5-hydroxymethylcytosine in mammalian development. Cell Res. 2011;21(9):1332–42. doi: 10.1038/cr.2011.113.PubMedPubMedCentralCrossRefGoogle Scholar
  97. Ryle MJ, Padmakumar R, Hausinger RP. Stopped-flow kinetic analysis of Escherichia coli taurine/alpha-ketoglutarate dioxygenase: interactions with alpha-ketoglutarate, taurine, and oxygen. Biochemistry. 1999;38(46):15278–86.PubMedCrossRefGoogle Scholar
  98. Saitou M, Kagiwada S, Kurimoto K. Epigenetic reprogramming in mouse pre-implantation development and primordial germ cells. Development. 2012;139(1):15–31. doi: 10.1242/dev.050849.PubMedCrossRefGoogle Scholar
  99. Schiesser S, Hackner B, Pfaffeneder T, Muller M, Hagemeier C, Truss M, et al. Mechanism and stem-cell activity of 5-carboxycytosine decarboxylation determined by isotope tracing. Angew Chem Int Ed Engl. 2012;51(26):6516–20. doi: 10.1002/anie.201202583.PubMedCrossRefGoogle Scholar
  100. Seisenberger S, Andrews S, Krueger F, Arand J, Walter J, Santos F, et al. The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell. 2012;48(6):849–62. doi: 10.1016/j.molcel.2012.11.001.PubMedPubMedCentralCrossRefGoogle Scholar
  101. Shen L, Kondo Y, Guo Y, Zhang J, Zhang L, Ahmed S, et al. Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters. PLoS Genet. 2007;3(10):2023–36. doi: 10.1371/journal.pgen.0030181.PubMedCrossRefGoogle Scholar
  102. Shen L, Wu H, Diep D, Yamaguchi S, D’Alessio AC, Fung HL, et al. Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics. Cell. 2013;153(3):692–706. doi: 10.1016/j.cell.2013.04.002.PubMedPubMedCentralCrossRefGoogle Scholar
  103. Shen L, Inoue A, He J, Liu YT, Lu FL, Zhang Y. Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes. Cell Stem Cell. 2014a;15(4):459–70. doi: 10.1016/J.Stem.2014.09.002.PubMedPubMedCentralCrossRefGoogle Scholar
  104. Shen L, Song CX, He C, Zhang Y. Mechanism and function of oxidative reversal of DNA and RNA methylation. Annu Rev Biochem. 2014b;83:585–614. doi: 10.1146/annurev-biochem-060713-035513.PubMedPubMedCentralCrossRefGoogle Scholar
  105. Shibata T, Kokubu A, Miyamoto M, Sasajima Y, Yamazaki N. Mutant IDH1 confers an in vivo growth in a melanoma cell line with BRAF mutation. Am J Pathol. 2011;178(3):1395–402. doi: 10.1016/j.ajpath.2010.12.011.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Smiley JA, Kundracik M, Landfried DA, Barnes Sr VR, Axhemi AA. 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. 2005;1723(1–3):256–64. doi: 10.1016/j.bbagen.2005.02.001.PubMedCrossRefGoogle Scholar
  107. Smith ZD, Meissner A. DNA methylation: roles in mammalian development. Nat Rev Genet. 2013;14(3):204–20. doi: 10.1038/nrg3354.PubMedCrossRefGoogle Scholar
  108. Song CX, Szulwach KE, Fu Y, Dai Q, Yi C, Li X, et al. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat Biotechnol. 2011;29(1):68–72. doi: 10.1038/nbt.1732.PubMedCrossRefGoogle Scholar
  109. Song CX, Szulwach KE, Dai Q, Fu Y, Mao SQ, Lin L, et al. Genome-wide profiling of 5-formylcytosine reveals its roles in epigenetic priming. Cell. 2013;153(3):678–91. doi: 10.1016/j.cell.2013.04.001.PubMedPubMedCentralCrossRefGoogle Scholar
  110. Szwagierczak A, Bultmann S, Schmidt CS, Spada F, Leonhardt H. Sensitive enzymatic quantification of 5-hydroxymethylcytosine in genomic DNA. Nucleic Acids Res. 2010;38(19):e181. doi: 10.1093/nar/gkq684.PubMedPubMedCentralCrossRefGoogle Scholar
  111. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930–5. doi: 10.1126/science.1170116.PubMedPubMedCentralCrossRefGoogle Scholar
  112. Tan L, Shi YG. Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development. 2012;139(11):1895–902. doi: 10.1242/dev.070771.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Tefferi A, Levine RL, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, et al. Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia. 2009;23(5):900–4. doi: 10.1038/leu.2009.37.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Tsai CL, Tainer JA. Probing DNA by 2-OG-dependent dioxygenase. Cell. 2013;155(7):1448–50. doi: 10.1016/j.cell.2013.12.002.PubMedPubMedCentralCrossRefGoogle Scholar
  115. Valegard K, van Scheltinga AC T, Dubus A, Ranghino G, Oster LM, Hajdu J, et al. The structural basis of cephalosporin formation in a mononuclear ferrous enzyme. Nat Struct Mol Biol. 2004;11(1):95–101. doi: 10.1038/nsmb712.PubMedCrossRefGoogle Scholar
  116. Valinluck V, Sowers LC. Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1. Cancer Res. 2007;67(3):946–50. doi: 10.1158/0008-5772.Can-06-3123.PubMedCrossRefGoogle Scholar
  117. Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC. 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. 2004;32(14):4100–8. doi: 10.1093/nar/gkh739.PubMedPubMedCentralCrossRefGoogle Scholar
  118. Vella P, Scelfo A, Jammula S, Chiacchiera F, Williams K, Cuomo A, et al. Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells. Mol Cell. 2013;49(4):645–56. doi: 10.1016/j.molcel.2012.12.019.PubMedCrossRefGoogle Scholar
  119. Wang T, Chen K, Zeng X, Yang J, Wu Y, Shi X, et al. The histone demethylases Jhdm1a/1b enhance somatic cell reprogramming in a vitamin-C-dependent manner. Cell Stem Cell. 2011;9(6):575–87. doi: 10.1016/j.stem.2011.10.005.PubMedCrossRefGoogle Scholar
  120. Wang L, Zhang J, Duan J, Gao X, Zhu W, Lu X, et al. Programming and inheritance of parental DNA methylomes in mammals. Cell. 2014;157(4):979–91. doi: 10.1016/j.cell.2014.04.017.PubMedPubMedCentralCrossRefGoogle Scholar
  121. Wang L, Zhou Y, Xu L, Xiao R, Lu X, Chen L, et al. Molecular basis for 5-carboxycytosine recognition by RNA polymerase II elongation complex. Nature. 2015a. doi: 10.1038/nature14482.Google Scholar
  122. Wang Y, Xiao M, Chen X, Chen L, Xu Y, Lv L, et al. WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation. Mol Cell. 2015b;57(4):662–73. doi: 10.1016/j.molcel.2014.12.023.PubMedPubMedCentralCrossRefGoogle Scholar
  123. Williams K, Christensen J, Pedersen MT, Johansen JV, Cloos PA, Rappsilber J, et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature. 2011;473(7347):343–8. doi: 10.1038/nature10066.PubMedPubMedCentralCrossRefGoogle Scholar
  124. Williams K, Christensen J, Helin K. DNA methylation: TET proteins-guardians of CpG islands? EMBO Rep. 2012;13(1):28–35. doi: 10.1038/embor.2011.233.CrossRefGoogle Scholar
  125. Wossidlo M, Nakamura T, Lepikhov K, Marques CJ, Zakhartchenko V, Boiani M, et al. 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nat Commun. 2011;2:241. doi: 10.1038/Ncomms1240. Artn 241.PubMedCrossRefGoogle Scholar
  126. Wu SC, Zhang Y. Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol. 2010;11(9):607–20. doi: 10.1038/nrm2950.PubMedPubMedCentralCrossRefGoogle Scholar
  127. Wu H, Zhang Y. Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation. Genes Dev. 2011;25(23):2436–52. doi: 10.1101/gad.179184.111.PubMedPubMedCentralCrossRefGoogle Scholar
  128. Wu H, Zhang Y. Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell. 2014;156(1–2):45–68. doi: 10.1016/j.cell.2013.12.019.PubMedPubMedCentralCrossRefGoogle Scholar
  129. Wu H, D’Alessio AC, Ito S, Xia K, Wang Z, Cui K, et al. Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature. 2011;473(7347):389–93. doi: 10.1038/nature09934.PubMedPubMedCentralCrossRefGoogle Scholar
  130. Xiao M, Yang H, Xu W, Ma S, Lin H, Zhu H, et al. Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 2012;26(12):1326–38. doi: 10.1101/gad.191056.112.PubMedPubMedCentralCrossRefGoogle Scholar
  131. Xie W, Barr CL, Kim A, Yue F, Lee AY, Eubanks J, et al. Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome. Cell. 2012;148(4):816–31. doi: 10.1016/j.cell.2011.12.035.PubMedPubMedCentralCrossRefGoogle Scholar
  132. Xu GL, Walsh CP. Enzymatic DNA oxidation: mechanisms and biological significance. BMB Rep. 2014;47(11):609–18.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011a;19(1):17–30. doi: 10.1016/j.ccr.2010.12.014.PubMedPubMedCentralCrossRefGoogle Scholar
  134. Xu Y, Wu F, Tan L, Kong L, Xiong L, Deng J, et al. Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells. Mol Cell. 2011b;42(4):451–64. doi: 10.1016/j.molcel.2011.04.005.PubMedPubMedCentralCrossRefGoogle Scholar
  135. Xu Y, Xu C, Kato A, Tempel W, Abreu JG, Bian C, et al. Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development. Cell. 2012;151(6):1200–13. doi: 10.1016/j.cell.2012.11.014.PubMedPubMedCentralCrossRefGoogle Scholar
  136. Xu S, Li W, Zhu J, Wang R, Li Z, Xu GL, et al. Crystal structures of isoorotate decarboxylases reveal a novel catalytic mechanism of 5-carboxyl-uracil decarboxylation and shed light on the search for DNA decarboxylase. Cell Res. 2013;23(11):1296–309. doi: 10.1038/cr.2013.107.PubMedPubMedCentralCrossRefGoogle Scholar
  137. Yamaguchi S, Hong K, Liu R, Shen L, Inoue A, Diep D, et al. Tet1 controls meiosis by regulating meiotic gene expression. Nature. 2012;492(7429):443–7. doi: 10.1038/nature11709.PubMedPubMedCentralCrossRefGoogle Scholar
  138. Yamaguchi S, Shen L, Liu Y, Sendler D, Zhang Y. Role of Tet1 in erasure of genomic imprinting. Nature. 2013;504(7480):460–4. doi: 10.1038/nature12805.PubMedPubMedCentralCrossRefGoogle Scholar
  139. Yamazaki Y, Mann MRW, Lee SS, Marh J, McCarrey JR, Yanagimachi R, et al. Reprogramming of primordial germ cells begins before migration into the genital ridge, making these cells inadequate donors for reproductive cloning. Proc Natl Acad Sci U S A. 2003;100(21):12207–12. doi: 10.1073/Pnas.2035119100.PubMedPubMedCentralCrossRefGoogle Scholar
  140. Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, et al. Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA. Nature. 2008;452(7190):961–5. doi: 10.1038/nature06889.PubMedPubMedCentralCrossRefGoogle Scholar
  141. Yang CG, Garcia K, He C. Damage detection and base flipping in direct DNA alkylation repair. Chembiochem Eur J Chem Biol. 2009;10(3):417–23. doi: 10.1002/cbic.200800580.CrossRefGoogle Scholar
  142. Yang H, Liu Y, Bai F, Zhang JY, Ma SH, Liu J, et al. Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation. Oncogene. 2013;32(5):663–9. doi: 10.1038/onc.2012.67.PubMedCrossRefGoogle Scholar
  143. Ye D, Ma S, Xiong Y, Guan KL. R-2-hydroxyglutarate as the key effector of IDH mutations promoting oncogenesis. Cancer Cell. 2013;23(3):274–6. doi: 10.1016/j.ccr.2013.03.005.PubMedPubMedCentralCrossRefGoogle Scholar
  144. Yildirim O, Li R, Hung JH, Chen PB, Dong X, Ee LS, et al. Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells. Cell. 2011;147(7):1498–510. doi: 10.1016/j.cell.2011.11.054.PubMedPubMedCentralCrossRefGoogle Scholar
  145. Yin R, Mao SQ, Zhao B, Chong Z, Yang Y, Zhao C, et al. Ascorbic acid enhances Tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals. J Am Chem Soc. 2013;135(28):10396–403. doi: 10.1021/ja4028346.PubMedCrossRefGoogle Scholar
  146. Young JI, Zuchner S, Wang G. Regulation of the Epigenome by Vitamin C. Annu Rev Nutr. 2015;35:545–64. doi: 10.1146/annurev-nutr-071714-034228.PubMedPubMedCentralCrossRefGoogle Scholar
  147. Yu Z, Genest PA, ter Riet B, Sweeney K, DiPaolo C, Kieft R, et al. The protein that binds to DNA base J in trypanosomatids has features of a thymidine hydroxylase. Nucleic Acids Res. 2007;35(7):2107–15. doi: 10.1093/Nar/Gkm049.PubMedPubMedCentralCrossRefGoogle Scholar
  148. Yu M, Hon GC, Szulwach KE, Song CX, Zhang L, Kim A, et al. Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome. Cell. 2012;149(6):1368–80. doi: 10.1016/j.cell.2012.04.027.PubMedPubMedCentralCrossRefGoogle Scholar
  149. Zhang L, Lu X, Lu J, Liang H, Dai Q, Xu GL, et al. Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA. Nat Chem Biol. 2012;8(4):328–30. doi: 10.1038/nchembio.914.PubMedPubMedCentralCrossRefGoogle Scholar
  150. Zhang G, Huang H, Liu D, Cheng Y, Liu X, Zhang W, et al. N6-methyladenine DNA modification in Drosophila. Cell. 2015;161(4):893–906. doi: 10.1016/j.cell.2015.04.018.PubMedCrossRefGoogle Scholar
  151. Zhou T, Xiong J, Wang M, Yang N, Wong J, Zhu B, et al. Structural basis for hydroxymethylcytosine recognition by the SRA domain of UHRF2. Mol Cell. 2014;54(5):879–86. doi: 10.1016/j.molcel.2014.04.003.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Fudan University Shanghai Cancer CenterInstitute of Biomedical Sciences, Shanghai Medical College of Fudan UniversityShanghaiChina
  2. 2.Key Laboratory of Molecular Medicine, Ministry of Education, Department of Systems Biology for MedicineSchool of Basic Medical Sciences, Shanghai Medical College of Fudan UniversityShanghaiChina
  3. 3.State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and DevelopmentSchool of Life Sciences, Fudan UniversityShanghaiChina

Personalised recommendations