Ten eleven translocation enzymes and 5-hydroxymethylation in mammalian development and cancer

Advances in Experimental Medicine and Biology

Volumn 754, Issue , 2013, Pages 57-79

  Kinney, Shannon R Morey ^a   Pradhan, Sriharsa ^a  

^a NEW ENGLAND BIOLABS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 HYDROXYMETHYLCYTOSINE; 5 METHYLCYTOSINE; CARRIER PROTEIN; TEN ELEVEN TRANSLOCATION ENZYME; UNCLASSIFIED DRUG;

5 HYDROXYMETHYLATION; ARTICLE; BRAIN; CANCER GROWTH; CARCINOGENESIS; CELL DIFFERENTIATION; DEMETHYLATION; DNA METHYLATION; DNA MODIFICATION; EMBRYO DEVELOPMENT; EMBRYONIC STEM CELL; ENZYME ACTIVITY; EPIGENETICS; GENE EXPRESSION REGULATION; GENE LOCUS; GENE MUTATION; HUMAN; MALIGNANT NEOPLASTIC DISEASE; MOUSE; NONHUMAN; OXIDATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION;

EID: 84869023648     PISSN: 00652598     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-4419-9967-2_3     Document Type: Article

References (107)

1. Bird AP (1986) CpG-rich islands and the function of DNA methylation. Nature 321:209-213 (Pubitemid 16016411)
2. Poulsen HE (2005) Oxidative DNA modi fi cations. Exp Toxicol Pathol 57(Suppl 1):161-169
3. Wu SC, Zhang Y (2010) Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol 11:607-620
4. Wyatt GR, Cohen SS (1952) A new pyrimidine base from bacteriophage nucleic acids. Nature 170:1072-1073
5. Josse J, Kornberg A (1962) Glucosylation of deoxyribonucleic acid III alpha- and beta-glucosyl transferases from T4-infected Escherichia coli. J Biol Chem 237:1968-1976
6. Kornberg SR, Zimmerman SB, Kornberg A (1961) Glucosylation of deoxyribonucleic acid by enzymes from bacteriophage-infected Escherichia coli. J Biol Chem 236:1487-1493
7. Penn NW, Suwalski R, O'Riley C, Bojanowski K, Yura R (1972) The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid. Biochem J 126:781-790
8. Penn NW (1976) Modi fi cation of brain deoxyribonucleic acid base content with maturation in normal and malnourished rats. Biochem J 155:709-712
9. Kothari RM, Shankar V (1976) 5-Methylcytosine content in the vertebrate deoxyribonucleic acids: species speci fi city. J Mol Evol 7:325-329
10. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930-935
11. Kriaucionis S, Heintz N (2009) The nuclear DNA base 5- hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324:929-930
12. Shock LS, Thakkar PV, Peterson EJ, Moran RG, Taylor SM (2011) DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria. Proc Natl Acad Sci USA 108:3630-3635
13. Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y (2002) LCX, leukemiaassociated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23). Cancer Res 62:4075-4080 (Pubitemid 34791077)
14. Lorsbach RB, Moore J, Mathew S, Raimondi SC, Mukatira ST, Downing JR (2003) TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia 17:637-641 (Pubitemid 36395661)
15. Loenarz C, Scho fi eld CJ (2009) Oxygenase catalyzed 5-methylcytosine hydroxylation. Chem Biol 16:580-583
16. Yu Z, Genest PA, ter Riet B, Sweeney K, DiPaolo C, Kieft R, Christodoulou E, Perrakis A, Simmons JM, Hausinger RP, van Luenen HG, Rigden DJ, Sabatini R, Borst P (2007) The protein that binds to DNA base J in trypanosomatids has features of a thymidine hydroxylase. Nucleic Acids Res 35:2107-2115 (Pubitemid 47073701)
17. Iyer LM, Tahiliani M, Rao A, Aravind L (2009) Prediction of novel families of enzymes involved in oxidative and other complex modi fi cations of bases in nucleic acids. Cell Cycle 8:1698-1710
18. Mohr F, Dohner K, Buske C, Rawat VP (2011) TET genes: new players in DNA demethylation and important determinants for stemness. Exp Hematol 39:272-281
19. Frauer C, Rottach A, Meilinger D, Bultmann S, Fellinger K, Hasenoder S, Wang M, Qin W, Soding J, Spada F, Leonhardt H (2011) Different binding properties and function of CXXC zinc fi nger domains in Dnmt1 and Tet1. PLoS One 6:e16627
20. Zhang H, Zhang X, Clark E, Mulcahey M, Huang S, Shi YG (2010) TET1 is a DNA-binding protein that modulates DNA methylation and gene transcription via hydroxylation of 5-methylcytosine. Cell Res 20:1390-1393
21. Ko M, Huang Y, Jankowska AM, Pape UJ, Tahiliani M, Bandukwala HS, An J, Lamperti ED, Koh KP, Ganetzky R, Liu XS, Aravind L, Agarwal S, Maciejewski JP, Rao A (2010) Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 468:839-843
22. 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 speci fi cation. Nature 466:1129-1133
23. Langemeijer SM, Aslanyan MG, Jansen JH (2009) TET proteins in malignant hematopoiesis. Cell Cycle 8:4044-4048
24. Langemeijer SM, Kuiper RP, Berends M, Knops R, Aslanyan MG, Massop M, Stevens- Linders E, van Hoogen P, van Kessel AG, Raymakers RA, Kamping EJ, Verhoef GE, Verburgh E, Hagemeijer A, Vandenberghe P, de Witte T, van der Reijden BA, Jansen JH (2009) Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet 41:838-842
25. Ficz G, Branco MR, Seisenberger S, Santos F, Krueger F, Hore TA, Marques CJ, Andrews S, Reik W (2011) Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 473:398-402
26. Globisch D, Munzel M, Muller M, Michalakis S, Wagner M, Koch S, Bruckl T, Biel M, Carell T (2010) Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. PLoS One 5:e15367
27. Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y (2011) Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333:1300-1303
28. He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L, Sun Y, Li X, Dai Q, Song CX, Zhang K, He C, Xu GL (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333:1303-1307
29. Huang Y, Pastor WA, Shen Y, Tahiliani M, Liu DR, Rao A (2010) The behaviour of 5-hydroxymethylcytosine in bisul fi te sequencing. PLoS One 5:e8888
30. Wang H, Guan S, Quimby A, Cohen-Karni D, Pradhan S, Wilson G, Roberts RJ, Zhu Z, Zheng Y (2011) Comparative characterization of the PvuRts1I family of restriction enzymes and their application in mapping genomic 5-hydroxymethylcytosine. Nucleic Acids Res 39:9294-9305
31. Song CX, Yu M, Dai Q, He C (2011) Detection of 5-hydroxymethylcytosine in a combined glycosylation restriction analysis (CGRA) using restriction enzyme Taq(alpha)I. Bioorg Med Chem Lett 21:5075-5077
32. Kinney SM, Chin HG, Vaisvila R, Bitinaite J, Zheng Y, Esteve PO, Feng S, Stroud H, Jacobsen SE, Pradhan S (2011) Tissue-speci fi c distribution and dynamic changes of 5-hydroxymethylcytosine in mammalian genomes. J Biol Chem 286:24685-24693
33. Szwagierczak A, Brachmann A, Schmidt CS, Bultmann S, Leonhardt H, Spada F (2011) Characterization of PvuRts1I endonuclease as a tool to investigate genomic 5-hydroxymethylcytosine. Nucleic Acids Res 39:5149-5156
34. Roberts RJ, Vincze T, Posfai J, Macelis D (2010) REBASE - a database for DNA restriction and modi fi cation: enzymes, genes and genomes. Nucleic Acids Res 38:D234-D236
35. Iqbal K, Jin SG, Pfeifer GP, Szabo PE (2011) Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc Natl Acad Sci USA 08:3642-3647
36. Stroud H, Feng S, Morey Kinney S, Pradhan S, Jacobsen SE (2011) 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells. Genome Biol 12:R54
37. Le T, Kim KP, Fan G, Faull KF (2011) A sensitive mass spectrometry method for simultaneous quanti fi cation of DNA methylation and hydroxymethylation levels in biological samples. Anal Biochem 412:203-209
38. Szwagierczak A, Bultmann S, Schmidt CS, Spada F, Leonhardt H (2010) Sensitive enzymatic quanti fi cation of 5-hydroxymethylcytosine in genomic DNA. Nucleic Acids Res 38:e181
39. Terragni J, Bitinaite J, Zheng Y, Pradhan S (2012) Biochemical characterization of recombinant Beta-glucosyltransferase and analysis of global 5-hydroxymethylcytosine in unique genomes. Biochemistry 51:1009-1019
40. Wu H, D'Alessio AC, Ito S, Wang Z, Cui K, Zhao K, Sun YE, Zhang Y (2011) Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes Dev 25:679-684
41. Wu H, D'Alessio AC, Ito S, Xia K, Wang Z, Cui K, Zhao K, Sun YE, Zhang Y (2011) Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature 473:389-393
42. Pastor WA, Pape UJ, Huang Y, Henderson HR, Lister R, Ko M, McLoughlin EM, Brudno Y, Mahapatra S, Kapranov P, Tahiliani M, Daley GQ, Liu XS, Ecker JR, Milos PM, Agarwal S, Rao A (2011) Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature 473:394-397
43. Song CX, Szulwach KE, Fu Y, Dai Q, Yi C, Li X, Li Y, Chen CH, Zhang W, Jian X, Wang J, Zhang L, Looney TJ, Zhang B, Godley LA, Hicks LM, Lahn BT, Jin P, He C (2011) Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat Biotechnol 29:68-72
44. Flusberg BA, Webster DR, Lee JH, Travers KJ, Olivares EC, Clark TA, Korlach J, Turner SW (2010) Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat Methods 7:461-465
45. Wanunu M, Cohen-Karni D, Johnson RR, Fields L, Benner J, Peterman N, Zheng Y, Klein ML, Drndic M (2010) Discrimination of methylcytosine from hydroxymethylcytosine in DNA molecules. J Am Chem Soc 133:486-492
46. Bair CL, Black LW (2007) A type IV modi fi cation dependent restriction nuclease that targets glucosylated hydroxymethyl cytosine modi fi ed DNAs. J Mol Biol 366:768-778 (Pubitemid 46175865)
47. Freudenberg JM, Ghosh S, Lackford BL, Yellaboina S, Zheng X, Li R, Cuddapah S, Wade PA, Hu G, Jothi R (2011) 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(8):3364-3377
48. Zhou GB, Meng QG, Li N (2010) In vitro derivation of germ cells from embryonic stem cells in mammals. Mol Reprod Dev 77:586-594
49. Koh KP, Yabuuchi A, Rao S, Huang Y, Cunniff K, Nardone J, Laiho A, Tahiliani M, Sommer CA, Mostoslavsky G, Lahesmaa R, Orkin SH, Rodig SJ, Daley GQ, Rao A (2011) Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage speci fi cation in mouse embryonic stem cells. Cell Stem Cell 8:200-213
50. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fi broblast cultures by defined factors. Cell 126:663-676 (Pubitemid 44233629)
51. Williams K, Christensen J, Pedersen MT, Johansen JV, Cloos PA, Rappsilber J, Helin K (2011) TET1 and hydroxymethylcytosine in transcription and DNA methylation fi delity. Nature 473:343-348
52. Xu Y, Wu F, Tan L, Kong L, Xiong L, Deng J, Barbera AJ, Zheng L, Zhang H, Huang S, Min J, Nicholson T, Chen T, Xu G, Shi Y, Zhang K, Shi YG (2011) Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells. Mol Cell 42:451-464
53. Dawlaty MM, Ganz K, Powell BE, Hu YC, Markoulaki S, Cheng AW, Gao Q, Kim J, Choi SW, Page DC, Jaenisch R (2011) Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development. Cell Stem Cell 9:166-175
54. Yildirim O, Li R, Hung JH, Chen PB, Dong X, Ee LS, Weng Z, Rando OJ, Fazzio TG (2011) Mbd3/NURD Complex Regulates Expression of 5- Hydroxymethylcytosine Marked Genes in Embryonic Stem Cells. Cell 147:1498-1510
55. Reik W, Dean W, Walter J (2001) Epigenetic reprogramming in mammalian development. Science 293:1089-1093 (Pubitemid 32758081)
56. Mayer W, Niveleau A, Walter J, Fundele R, Haaf T (2000) Demethylation of the zygotic paternal genome. Nature 403:501-502 (Pubitemid 30082186)
57. Oswald J, Engemann S, Lane N, Mayer W, Olek A, Fundele R, Dean W, Reik W, Walter J (2000) Active demethylation of the paternal genome in the mouse zygote. Curr Biol 10:475-478 (Pubitemid 30247337)
58. Santos F, Hendrich B, Reik W, Dean W (2002) Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol 241:172-182 (Pubitemid 34066770)
59. 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
60. Wossidlo M, Nakamura T, Lepikhov K, Marques CJ, Zakhartchenko V, Boiani M, Arand J, Nakano T, Reik W, Walter J (2011) 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nat Commun 2:241
61. Gu TP, Guo F, Yang H, Wu HP, Xu GF, Liu W, Xie ZG, Shi L, He X, Jin SG, Iqbal K, Shi YG, Deng Z, Szabo PE, Pfeifer GP, Li J, Xu GL (2011) The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477:606-610
62. Nakamura T, Arai Y, Umehara H, Masuhara M, Kimura T, Taniguchi H, Sekimoto T, Ikawa M, Yoneda Y, Okabe M, Tanaka S, Shiota K, Nakano T (2007) PGC7/Stella protects against DNA demethylation in early embryogenesis. Nat Cell Biol 9:64-71 (Pubitemid 46024198)
63. Quivoron C, Couronne L, Della Valle V, Lopez CK, Plo I, Wagner-Ballon O, Do Cruzeiro M, Delhommeau F, Arnulf B, Stern MH, Godley L, Opolon P, Tilly H, Solary E, Duffourd Y, Dessen P, Merle-Beral H, Nguyen-Khac F, Fontenay M, Vainchenker W, Bastard C, Mercher T, Bernard OA (2011) TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell 20:25-38
64. Kraus TF, Globisch D, Wagner M, Eigenbrod S, Widmann D, Munzel M, Muller M, Pfaffeneder T, Hackner B, Feiden W, Schuller U, Carell T, Kretzschmar HA (2012) Low values of 5-hydroxymethylcytosine (5hmC), the "sixth base", are associated with anaplasia in human brain tumours. International journal of cancer. J Int Cancer Jan 10. doi: 10.1002/ ijc.27429. [Epub ahead of print]
65. Burmeister T, Meyer C, Schwartz S, Hofmann J, Molkentin M, Kowarz E, Schneider B, Raff T, Reinhardt R, Gokbuget N, Hoelzer D, Thiel E, Marschalek R (2009) The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group. Blood 113:4011-4015
66. Pui CH, Chessells JM, Camitta B, Baruchel A, Biondi A, Boyett JM, Carroll A, Eden OB, Evans WE, Gadner H, Harbott J, Harms DO, Harrison CJ, Harrison PL, Heerema N, Janka- Schaub G, Kamps W, Masera G, Pullen J, Raimondi SC, Richards S, Riehm H, Sallan S, Sather H, Shuster J, Silverman LB, Valsecchi MG, Vilmer E, Zhou Y, Gaynon PS, Schrappe M (2003) Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements. Leukemia 17:700-706 (Pubitemid 36519366)
67. Pui CH, Gaynon PS, Boyett JM, Chessells JM, Baruchel A, Kamps W, Silverman LB, Biondi A, Harms DO, Vilmer E, Schrappe M, Camitta B (2002) Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region. Lancet 359:1909-1915 (Pubitemid 34615770)
68. Liedtke M, Cleary ML (2009) Therapeutic targeting of MLL. Blood 113:6061-6068
69. Chou WC, Chou SC, Liu CY, Chen CY, Hou HA, Kuo YY, Lee MC, Ko BS, Tang JL, Yao M, Tsay W, Wu SJ, Huang SY, Hsu SC, Chen YC, Chang YC, Kuo KT, Lee FY, Liu MC, Liu CW, Tseng MH, Huang CF, Tien HF (2011) TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia patients with intermediate-risk cytogenetics. Blood 118:3803-3810
70. Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A, Kosmider O, Le Couedic JP, Robert F, Alberdi A, Lecluse Y, Plo I, Dreyfus FJ, Marzac C, Casadevall N, Lacombe C, Romana SP, Dessen P, Soulier J, Viguie F, Fontenay M, Vainchenker W, Bernard OA (2009) Mutation in TET2 in myeloid cancers. N Engl J Med 360:2289-2301
71. Tefferi A, Levine RL, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Finke CM, Mullally A, Li CY, Pardanani A, Gilliland DG (2009) Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia 23:900-904
72. Tefferi A, Lim KH, Levine R (2009) Mutation in TET2 in myeloid cancers. N Engl J Med 361:1117
73. Tefferi A, Pardanani A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Gangat N, Finke CM, Schwager S, Mullally A, Li CY, Hanson CA, Mesa R, Bernard O, Delhommeau F, Vainchenker W, Gilliland DG, Levine RL (2009) TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelo fi brosis. Leukemia 23:905-911
74. Tefferi A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Patnaik MM, Hanson CA, Pardanani A, Gilliland DG, Levine RL (2009) Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML. Leukemia 23: 1343-1345
75. Makishima H, Jankowska AM, McDevitt MA, O'Keefe C, Dujardin S, Cazzolli H, Przychodzen B, Prince C, Nicoll J, Siddaiah H, Shaik M, Szpurka H, Hsi E, Advani A, Paquette R, Maciejewski JP (2011) CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia. Blood 117:e198-e206
76. Jardin F, Ruminy P, Parmentier F, Troussard X, Vaida I, Stamatoullas A, Lepretre S, Penther D, Duval AB, Picquenot JM, Courville P, Capiod JC, Tilly H, Bastard C, Marolleau JP (2011) TET2 and TP53 mutations are frequently observed in blastic plasmacytoid dendritic cell neoplasm. Br J Haematol 153:413-416
77. Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, Patel J, Wadleigh M, Malinge S, Yao J, Kilpivaara O, Bhat R, Huberman K, Thomas S, Dolgalev I, Heguy A, Paietta E, Le Beau MM, Beran M, Tallman MS, Ebert BL, Kantarjian HM, Stone RM, Gilliland DG, Crispino JD, Levine RL (2009) Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood 114:144-147
78. Jankowska AM, Szpurka H, Tiu RV, Makishima H, Afable M, Huh J, O'Keefe CL, Ganetzky R, McDevitt MA, Maciejewski JP (2009) Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood 113:6403-6410
79. Kosmider O, Gelsi-Boyer V, Cheok M, Grabar S, Della-Valle V, Picard F, Viguie F, Quesnel B, Beyne-Rauzy O, Solary E, Vey N, Hunault-Berger M, Fenaux P, Mansat-De Mas V, Delabesse E, Guardiola P, Lacombe C, Vainchenker W, Preudhomme C, Dreyfus F, Bernard OA, Birnbaum D, Fontenay M (2009) TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs). Blood 114:3285-3291
80. Kosmider O, Gelsi-Boyer V, Ciudad M, Racoeur C, Jooste V, Vey N, Quesnel B, Fenaux P, Bastie JN, Beyne-Rauzy O, Stamatoulas A, Dreyfus F, Ifrah N, de Botton S, Vainchenker W, Bernard OA, Birnbaum D, Fontenay M, Solary E (2009) TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia. Haematologica 94:1676-1681
81. Kohlmann A, Grossmann V, Klein HU, Schindela S, Weiss T, Kazak B, Dicker F, Schnittger S, Dugas M, Kern W, Haferlach C, Haferlach T (2010) Next-generation sequencing technology reveals a characteristic pattern of molecular mutations in 72.8% of chronic myelomonocytic leukemia by detecting frequent alterations in TET2, CBL, RAS, and RUNX1. J Clin Oncol 28:3858-3865
82. Nibourel O, Kosmider O, Cheok M, Boissel N, Renneville A, Philippe N, Dombret H, Dreyfus F, Quesnel B, Geffroy S, Quentin S, Roche-Lestienne C, Cayuela JM, Roumier C, Fenaux P, Vainchenker W, Bernard OA, Soulier J, Fontenay M, Preudhomme C (2010) Incidence and prognostic value of TET2 alterations in de novo acute myeloid leukemia achieving complete remission. Blood 116:1132-1135
83. Hellstrom-Lindberg E (2010) Signi fi cance of JAK2 and TET2 mutations in myelodysplastic syndromes. Blood Rev 24:83-90
84. Swierczek SI, Yoon D, Bellanne-Chantelot C, Kim SJ, Saint-Martin C, Delhommeau F, Najman A, Prchal JT (2011) Extent of hematopoietic involvement by TET2 mutations in JAK2V(1)F polycythemia vera. Haematologica 96:775-778
85. Rocquain J, Carbuccia N, Trouplin V, Raynaud S, Murati A, Nezri M, Tadrist Z, Olschwang S, Vey N, Birnbaum D, Gelsi-Boyer V, Mozziconacci MJ (2010) Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias. BMC Cancer 10:401
86. Ko M, Bandukwala HS, An J, Lamperti ED, Thompson EC, Hastie R, Tsangaratou A, Rajewsky K, Koralov SB, Rao A (2011) Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice. Proc Natl Acad Sci USA 108:14566-14571
87. Gelsi-Boyer V, Trouplin V, Adelaide J, Bonansea J, Cervera N, Carbuccia N, Lagarde A, Prebet T, Nezri M, Sainty D, Olschwang S, Xerri L, Chaffanet M, Mozziconacci MJ, Vey N, Birnbaum D (2009) Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol 145:788-800
88. Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez HF, Tallman MS, Sun Z, Wolniak K, Peeters JK, Liu W, Choe SE, Fantin VR, Paietta E, Lowenberg B, Licht JD, Godley LA, Delwel R, Valk PJ, Thompson CB, Levine RL, Melnick A (2010) Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18:553-567
89. Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden MG, Su SM (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739-744
90. Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA, Cross JR, Fantin VR, Hedvat CV, Perl AE, Rabinowitz JD, Carroll M, Su SM, Sharp KA, Levine RL, Thompson CB (2010) The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17:225-234
91. Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Xiao MT, Liu LX, Jiang WQ, Liu J, Zhang JY, Wang B, Frye S, Zhang Y, Xu YH, Lei QY, Guan KL, Zhao SM, Xiong Y (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutaratedependent dioxygenases. Cancer Cell 19:17-30
92. Haffner MC, Chaux A, Meeker AK, Esopi DM, Gerber J, Pellakuru LG, Toubaji A, Argani P, Iacobuzio-Donahue C, Nelson WG, Netto GJ, De Marzo AM, Yegnasubramanian S (2011) Global 5-hydroxymethylcytosine content is signi fi cantly reduced in tissue stem/progenitor cell compartments and in human cancers. Oncotarget 2:627-637
93. Li W, Liu M (2011) Distribution of 5-hydroxymethylcytosine in different human tissues. J Nucleic Acids 2011:870726
94. Kantarjian H, O'Brien S, Cortes J, Wierda W, Faderl S, Garcia-Manero G, Issa JP, Estey E, Keating M, Freireich EJ (2008) Therapeutic advances in leukemia and myelodysplastic syndrome over the past 40 years. Cancer 113:1933-1952
95. Pollyea DA, Raval A, Kusler B, Gotlib JR, Alizadeh AA, Mitchell BS (2010) Impact of TET2 mutations on mRNA expression and clinical outcomes in MDS patients treated with DNA methyltransferase inhibitors. Hematol Oncol 29:157-160
96. Itzykson R, Kosmider O, Cluzeau T, Mansat-De Mas V, Dreyfus F, Beyne-Rauzy O, Quesnel B, Vey N, Gelsi-Boyer V, Raynaud S, Preudhomme C, Ades L, Fenaux P, Fontenay M (2011) Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia 25:1147-1152
97. Detich N, Theberge J, Szyf M (2002) Promoter-speci fi c activation and demethylation by MBD2/demethylase. J Biol Chem 277:35791-35794
98. Feng S, Jacobsen SE, Reik W (2010) Epigenetic reprogramming in plant and animal development. Science 330:622-627
99. Metivier R, Gallais R, Tiffoche C, Le Peron C, Jurkowska RZ, Carmouche RP, Ibberson D, Barath P, Demay F, Reid G, Benes V, Jeltsch A, Gannon F, Salbert G (2008) Cyclical DNA methylation of a transcriptionally active promoter. Nature 452:45-50 (Pubitemid 351355084)
100. Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC (2004) 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 32:4100-4108 (Pubitemid 39232282)
101. Valinluck V, Sowers LC (2007) Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1. Cancer Res 67:946-950
102. Cannon SV, Cummings A, Teebor GW (1988) 5-Hydroxymethylcytosine DNA glycosylase activity in mammalian tissue. Biochem Biophys Res Commun 151:1173-1179 (Pubitemid 18095244)
103. 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 145:423-434
104. Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H (2009) Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323:1074-1077
105. Maiti A, Drohat AC (2011) Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: Potential implications for active demethylation of CpG sites. J Biol Chem 286:35334-35338
106. Booth MJ, Branco MR, Ficz G, Oxley D, Krueger F, Reik W, Balasubramanian S. (2012) Quantitative sequencing of 5-methylcytosine and 5- hydroxymethylcytosine at single-base resolution. Science 336:934-937
107. Yu M, Hon GC, Szulwach KE, Song CX, Zhang L, Kim A, Li X, Dai Q, Shen Y, Park B, Min JH, Jin P, Ren B, He C (2012) Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome. Cell 149:1368-1380