Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA methylation

Pharmacology and Therapeutics

Volumn 151, Issue , 2015, Pages 121-140

  Liu, Ke ^a,b   Liu, Yanli ^a,b   Lau, Johnathan L ^b,c   Min, Jinrong ^a,b,c  

^a CENTRAL CHINA NORMAL UNIVERSITY   (China)

^b UNIVERSITY OF TORONTO   (Canada)

^c UNIVERSITY OF TORONTO   (Canada)

Author keywords

Chemical probe; DNA methylation; Drug discovery; Histone demethylation; Inhibitor

Indexed keywords

DNA METHYLTRANSFERASE; DNA METHYLTRANSFERASE INHIBITOR; HISTONE; HISTONE DEMETHYLASE; HISTONE METHYLLYSINE; HISTONE METHYLTRANSFERASE; LYSINE DERIVATIVE; PROTEIN KDM2; PROTEIN KDM4; PROTEIN KDM5; PROTEIN KDM6; PROTEIN LSD1; PROTEIN LSD2; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT;

ARTICLE; CHROMATIN STRUCTURE; CLINICAL TRIAL (TOPIC); DNA METHYLATION; DRUG PROTEIN BINDING; DRUG SYNTHESIS; DRUG TARGETING; EPIGENETICS; HISTONE DEMETHYLATION; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN FAMILY; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; ENZYMOLOGY; GENETIC EPIGENESIS; METABOLISM; NEOPLASMS; PROTEIN CONFORMATION;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; DNA METHYLATION; DNA MODIFICATION METHYLASES; DRUG DISCOVERY; EPIGENESIS, GENETIC; HISTONE DEMETHYLASES; HUMANS; JUMONJI DOMAIN-CONTAINING HISTONE DEMETHYLASES; MODELS, MOLECULAR; NEOPLASMS; PROTEIN CONFORMATION;

EID: 84930212511     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2015.04.001     Document Type: Review

References (239)

1. U. Aapola, I. Liiv, and P. Peterson Imprinting regulator DNMT3L is a transcriptional repressor associated with histone deacetylase activity Nucleic Acids Res 30 16 2002 3602 3608
2. K. Agger, P.A. Cloos, J. Christensen, D. Pasini, S. Rose, and J. Rappsilber UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development Nature 449 7163 2007 731 734
3. K. Agger, P.A. Cloos, L. Rudkjær, K. Williams, G. Andersen, and J. Christensen The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene-and stress-induced senescence Genes Dev 23 10 2009 1171 1176
4. S. Agrawal, and R.P. Iyer Perspectives in antisense therapeutics Pharmacol Ther 76 1 1997 151 160
5. A.I. Agulnik, M.J. Mitchell, J.L. Lerner, D.R. Woods, and C.E. Bishop A mouse Y chromosome gene encoded by a region essential for spermatogenesis and expression of male-specific minor histocompatibility antigens Hum Mol Genet 3 6 1994 873 878
6. R.J. Amato Inhibition of DNA methylation by antisense oligonucleotide MG98 as cancer therapy Clin Genitourin Cancer 5 7 2007 422 426
7. A. Barrett, S. Santangelo, K. Tan, S. Catchpole, K. Roberts, and B. Spencer Dene Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases Int J Cancer 121 2 2007 265 275
8. J.A. Beisler, M.M. Abbasi, and J.S. Driscoll Synthesis and antitumor activity of 5-azacytosine arabinoside J Med Chem 22 10 1979 1230 1234
9. J.A. Beisler, M.M. Abbasi, J.A. Kelley, and J.S. Driscoll Synthesis and antitumor activity of dihydro-5-azacytidine, a hydrolytically stable analog of 5-azacytidine J Med Chem 20 6 1977 806 812
10. N. Ben-Baruch, A.M. Denicoff, B.R. Goldspiel, J.A. O'Shaughnessy, and K.H. Cowan Phase II study of fazarabine (NSC 281272) in patients with metastatic colon cancer Invest New Drugs 11 1 1993 71 74
11. B. Berdel, K. Nieminen, Y. Soini, M. Tengström, M. Malinen, and V. Kosma Histone demethylase GASC1-a potential prognostic and predictive marker in invasive breast cancer BMC Cancer 12 1 2012 516
12. W.L. Berry, and R. Janknecht KDM4/JMJD2 histone demethylases: Epigenetic regulators in cancer cells Cancer Res 73 10 2013 2936 2942
13. W.L. Berry, S. Shin, S.A. Lightfoot, and R. Janknecht Oncogenic features of the JMJD2A histone demethylase in breast cancer Int J Oncol 41 5 2012 1701 1706
14. C. Binda, S. Valente, M. Romanenghi, S. Pilotto, R. Cirilli, and A. Karytinos Biochemical, structural, and biological evaluation of tranylcypromine derivatives as inhibitors of histone demethylases LSD1 and LSD2 J Am Chem Soc 132 19 2010 6827 6833
15. D. Biswas, T.A. Milne, V. Basrur, J. Kim, K.S. Elenitoba-Johnson, and C.D. Allis Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes Proc Natl Acad Sci U S A 108 38 2011 15751 15756
16. M. Bostick, J.K. Kim, P. Estève, A. Clark, S. Pradhan, and S.E. Jacobsen UHRF1 plays a role in maintaining DNA methylation in mammalian cells Science 317 5845 2007 1760 1764
17. C.J. Brown, A.P. Miller, L. Carrel, J.L. Rupert, K.E. Davies, and H.F. Willard The DXS423E gene in Xp11. 21 escapes X chromosome inactivation Hum Mol Genet 4 2 1995 251 255
18. B. Brueckner, R.G. Boy, P. Siedlecki, T. Musch, H.C. Kliem, and P. Zielenkiewicz Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases Cancer Res 65 14 2005 6305 6311
19. B. Brueckner, M. Rius, M.R. Markelova, I. Fichtner, P. Hals, and M.L. Sandvold Delivery of 5-azacytidine to human cancer cells by elaidic acid esterification increases therapeutic drug efficacy Mol Cancer Ther 9 5 2010 1256 1264
20. J. Bryan, H. Kantarjian, G. Garcia-Manero, and E. Jabbour Pharmacokinetic evaluation of decitabine for the treatment of leukemia Expert Opin Drug Metab Toxicol 7 5 2011 661 672
21. H. Byun, S.H. Choi, P.W. Laird, B. Trinh, M.A. Siddiqui, and V.E. Marquez 2′-Deoxy-N4-[2-(4-nitrophenyl) ethoxycarbonyl]-5-azacytidine: A novel inhibitor of DNA methyltransferase that requires activation by human carboxylesterase 1 Cancer Lett 266 2 2008 238 248
22. C. Cai, H.H. He, S. Gao, S. Chen, Z. Yu, and Y. Gao Lysine-specific demethylase 1 has dual functions as a major regulator of androgen receptor transcriptional activity Cell Rep 9 5 2014 1618 1627
23. E.S. Casper, G.K. Schwartz, and D.P. Kelsen Phase II trial of fazarabine (arabinofuranosyl-5-azacytidine) in patients with advanced pancreatic adenocarcinoma Invest New Drugs 10 3 1992 205 209
24. K.H. Chang, O.N. King, A. Tumber, E.C. Woon, T.D. Heightman, and M.A. McDonough Inhibition of histone demethylases by 4-carboxy-2, 2′-bipyridyl compounds ChemMedChem 6 5 2011 759 764
25. F. Chédin, M.R. Lieber, and C. Hsieh The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a Proc Natl Acad Sci U S A 99 26 2002 16916 16921
26. Z.X. Chen, J.R. Mann, C.L. Hsieh, A.D. Riggs, and F. Chédin Physical and functional interactions between the human DNMT3L protein and members of the de novo methyltransferase family J Cell Biochem 95 5 2005 902 917
27. Z. Cheng, P. Cheung, A.J. Kuo, E.T. Yukl, C.M. Wilmot, and O. Gozani A molecular threading mechanism underlies Jumonji lysine demethylase KDM2A regulation of methylated H3K36 Genes Dev 28 16 2014 1758 1771
28. J.C. Cheng, C.B. Matsen, F.A. Gonzales, W. Ye, S. Greer, and V.E. Marquez Inhibition of DNA methylation and reactivation of silenced genes by zebularine J Natl Cancer Inst 95 5 2003 399 409
29. J.C. Cheng, C.B. Yoo, D.J. Weisenberger, J. Chuang, C. Wozniak, and G. Liang Preferential response of cancer cells to zebularine Cancer Cell 6 2 2004 151 158
30. Y. Cho, T. Hong, S. Hong, H. Guo, H. Yu, and D. Kim PTIP associates with MLL3-and MLL4-containing histone H3 lysine 4 methyltransferase complex J Biol Chem 282 28 2007 20395 20406
31. C. Chu, L. Wang, K. Hsu, C. Chen, H. Cheng, and S. Wang KDM4B as a target for prostate cancer: Structural analysis and selective inhibition by a novel inhibitor J Med Chem 57 14 2014 5975 5985
32. J.C. Chuang, S.L. Warner, D. Vollmer, H. Vankayalapati, S. Redkar, and D.J. Bearss S110, a 5-Aza-2′-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth Mol Cancer Ther 9 5 2010 1443 1450
33. J.C. Chuang, C.B. Yoo, J.M. Kwan, T.W. Li, G. Liang, and A.S. Yang Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2′-deoxycytidine Mol Cancer Ther 4 10 2005 1515 1520
34. P.A. Cloos, J. Christensen, K. Agger, and K. Helin Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease Genes Dev 22 9 2008 1115 1140
35. P.A. Cloos, J. Christensen, K. Agger, A. Maiolica, J. Rappsilber, and T. Antal The putative oncogene GASC1 demethylates tri-and dimethylated lysine 9 on histone H3 Nature 442 7100 2006 307 311
36. P.G. Constantinides, P.A. Jones, and W. Gevers Functional striated muscle cells from non-myoblast precursors following 5-azacytidine treatment Nature 267 5609 1977 364 366
37. L. Couronné, C. Bastard, and O.A. Bernard TET2 and DNMT3A mutations in human T-cell lymphoma N Engl J Med 366 1 2012 95 96
38. E.T. Creagan, D.J. Schaid, L.C. Hartmann, and C.L. Loprinzi A phase II study of 5, 6-dihydro-5-azacytidine hydrochloride in disseminated malignant melanoma Am J Clin Oncol 16 3 1993 243 244
39. J.C. Culhane, L.M. Szewczuk, X. Liu, G. Da, R. Marmorstein, and P.A. Cole A mechanism-based inactivator for histone demethylase LSD1 J Am Chem Soc 128 14 2006 4536 4537
40. C. Curtis, S.P. Shah, S. Chin, G. Turashvili, O.M. Rueda, and M.J. Dunning The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups Nature 486 7403 2012 346 352
41. G.L. Dalgliesh, K. Furge, C. Greenman, L. Chen, G. Bignell, and A. Butler Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes Nature 463 7279 2010 360 363
42. J. Datta, K. Ghoshal, W.A. Denny, S.A. Gamage, D.G. Brooke, and P. Phiasivongsa A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation Cancer Res 69 10 2009 4277 4285
43. S. Davidson, P. Crowther, J. Radley, and D. Woodcock Cytotoxicity of 5-aza-2′-deoxycytidine in a mammalian cell system Eur J Cancer 28 2 1992 362 368
44. A.J. Davis, K.A. Gelmon, L.L. Siu, M.J. Moore, C.D. Britten, and N. Mistry Phase I and pharmacologic study of the human DNA methyltransferase antisense oligodeoxynucleotide MG98 given as a 21-day continuous infusion every 4 weeks Invest New Drugs 21 1 2003 85 97
45. F. De Santa, M.G. Totaro, E. Prosperini, S. Notarbartolo, G. Testa, and G. Natoli The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing Cell 130 6 2007 1083 1094
46. Y. Delpu, P. Cordelier, W.C. Cho, and J. Torrisani DNA methylation and cancer diagnosis Int J Mol Sci 14 7 2013 15029 15058
47. C. Deng, Q. Lu, Z. Zhang, T. Rao, J. Attwood, and R. Yung Hydralazine may induce autoimmunity by inhibiting extracellular signal-regulated kinase pathway signaling Arthritis Rheum 48 3 2003 746 756
48. R. Dong, R. Yao, J. Du, S. Wang, and Z. Fan Depletion of histone demethylase KDM2A enhanced the adipogenic and chondrogenic differentiation potentials of stem cells from apical papilla Exp Cell Res 319 18 2013 2874 2882
49. C. Dong, H. Zhang, C. Xu, C.H. Arrowsmith, and J. Min Structure and function of dioxygenases in histone demethylation and DNA/RNA demethylation IUCrJ 1 6 2014 540 549
50. B. Dulla, K.T. Kirla, V. Rathore, G.S. Deora, S. Kavela, and S. Maddika Synthesis and evaluation of 3-amino/guanidine substituted phenyl oxazoles as a novel class of LSD1 inhibitors with anti-proliferative properties Org Biomol Chem 11 19 2013 3103 3107
51. K. Eguchi, Y. Kanai, K. Kobayashi, and S. Hirohashi DNA hypermethylation at the D17S5 locus in non-small cell lung cancers: its association with smoking history Cancer Res 57 21 1997 4913 4915
52. J. Fahy, A. Jeltsch, and P.B. Arimondo DNA methyltransferase inhibitors in cancer: A chemical and therapeutic patent overview and selected clinical studies Expert Opin Ther Pat 22 12 2012 1427 1442
53. R. Fang, A.J. Barbera, Y. Xu, M. Rutenberg, T. Leonor, and Q. Bi Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation Mol Cell 39 2 2010 222 233
54. M.Z. Fang, D. Chen, Y. Sun, Z. Jin, J.K. Christman, and C.S. Yang Reversal of hypermethylation and reactivation of p16INK4a, RARβ, and MGMT genes by genistein and other isoflavones from soy Clin Cancer Res 11 19 2005 7033 7041
55. F. Fang, J. Munck, J. Tang, P. Taverna, Y. Wang, and D.F. Miller The novel, small-molecule DNA methylation inhibitor SGI-110 as an ovarian cancer chemosensitizer Clin Cancer Res 20 24 2014 6504 6516
56. M.Z. Fang, Y. Wang, N. Ai, Z. Hou, Y. Sun, and H. Lu Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines Cancer Res 63 22 2003 7563 7570
57. A. Finley, and R.A. Copeland Small molecule control of chromatin remodeling Chem Biol 21 9 2014 1196 1210
58. W. Fiskus, S. Sharma, B. Shah, B.P. Portier, S. Devaraj, and K. Liu Highly effective combination of LSD1 (KDM1A) antagonist and pan-histone deacetylase inhibitor against human AML cells Leukemia 28 11 2014 2155 2164
59. D. Frescas, D. Guardavaccaro, F. Bassermann, R. Koyama-Nasu, and M. Pagano JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes Nature 450 7167 2007 309 313
60. D. Frescas, D. Guardavaccaro, S.M. Kuchay, H. Kato, A. Poleshko, and V. Basrur KDM2A represses transcription of centromeric satellite repeats and maintains the heterochromatic state Cell Cycle 7 22 2008 3539 3547
61. I. Garcia-Bassets, Y. Kwon, F. Telese, G.G. Prefontaine, K.R. Hutt, and C.S. Cheng Histone methylation-dependent mechanisms impose ligand dependency for gene activation by nuclear receptors Cell 128 3 2007 505 518
62. R. Garzon, C.E. Heaphy, V. Havelange, M. Fabbri, S. Volinia, and T. Tsao MicroRNA 29b functions in acute myeloid leukemia Blood 114 26 2009 5331 5341
63. J. Goffin, and E. Eisenhauer DNA methyltransferase inhibitors - state of the art Ann Oncol 13 11 2002 1699 1716
64. S.G. Gray, A.H. Iglesias, F. Lizcano, R. Villanueva, S. Camelo, and H. Jingu Functional characterization of JMJD2A, a histone deacetylase-and retinoblastoma-binding protein J Biol Chem 280 31 2005 28507 28518
65. Guibourt, N., Munoz, A. O., & Laria, J. C. (2010). Phenylcyclopropylamine derivatives and their medical use: Google Patents.
66. W.J. Harris, X. Huang, J.T. Lynch, G.J. Spencer, J.R. Hitchin, and Y. Li The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells Cancer Cell 21 4 2012 473 487
67. T. Hayakawa, and J. Nakayama Physiological roles of class I HDAC complex and histone demethylase J Biomed Biotechnol 2010 10.1155/2011/129383
68. T. Hayakawa, Y. Ohtani, N. Hayakawa, K. Shinmyozu, M. Saito, and F. Ishikawa RBP2 is an MRG15 complex component and down-regulates intragenic histone H3 lysine 4 methylation Genes Cells 12 6 2007 811 826
69. S. Hayami, J.D. Kelly, H.S. Cho, M. Yoshimatsu, M. Unoki, and T. Tsunoda Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers Int J Cancer 128 3 2011 574 586
70. S. Hayami, M. Yoshimatsu, A. Veerakumarasivam, M. Unoki, Y. Iwai, and T. Tsunoda Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway Mol Cancer 9 59 2010 10.1186/1476-4598-9-59
71. M. Heidenblad, D. Lindgren, T. Jonson, F. Liedberg, S. Veerla, and G. Chebil Tiling resolution array CGH and high density expression profiling of urothelial carcinomas delineate genomic amplicons and candidate target genes specific for advanced tumors BMC Med Genomics 2008 10.1186/1755-8794-1-3
72. B. Heinemann, J.M. Nielsen, H.R. Hudlebusch, M.J. Lees, D.V. Larsen, and T. Boesen Inhibition of demethylases by GSK-J1/J4 Nature 514 7520 2014 E1 E2
73. K. Helin, and D. Dhanak Chromatin proteins and modifications as drug targets Nature 502 7472 2013 480 488
74. L. Hillringhaus, W.W. Yue, N.R. Rose, S.S. Ng, C. Gileadi, and C. Loenarz Structural and evolutionary basis for the dual substrate selectivity of human KDM4 histone demethylase family J Biol Chem 286 48 2011 41616 41625
75. J.R. Hitchin, J. Blagg, R. Burke, S. Burns, M.J. Cockerill, and E.E. Fairweather Development and evaluation of selective, reversible LSD1 inhibitors derived from fragments Med Chem Commun 4 11 2013 1513 1522
76. S. Ho Environmental epigenetics of asthma: An update J Allergy Clin Immunol 126 3 2010 453 465
77. P.Y. Holoye, H.M. Dhingra, T. Umsawasdi, W.K. Murphy, D.T. Carr, and J.S. Lee Phase II study of 5, 6-dihydro-5-azacytidine in extensive, untreated non-small cell lung cancer Cancer Treat Rep 71 9 1987 859 860
78. P. Huang, C. Chen, C. Chou, A.M. Sargeant, S.K. Kulp, and C. Teng Histone deacetylase inhibitors stimulate histone H3 lysine 4 methylation in part via transcriptional repression of histone H3 lysine 4 demethylases Mol Pharmacol 79 1 2011 197 206
79. Y. Huang, E. Greene, T.M. Stewart, A.C. Goodwin, S.B. Baylin, and P.M. Woster Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes Proc Natl Acad Sci U S A 104 19 2007 8023 8028
80. Y. Huang, Y. Liu, L. Yu, J. Chen, J. Hou, and L. Cui Histone demethylase KDM2A promotes tumor cell growth and migration in gastric cancer Tumor Biol 36 1 2015 271 278
81. L. Isakovic, O.M. Saavedra, D.B. Llewellyn, S. Claridge, L. Zhan, and N. Bernstein Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors Bioorg Med Chem Lett 19 10 2009 2742 2746
82. I. Issaeva, Y. Zonis, T. Rozovskaia, K. Orlovsky, C.M. Croce, and T. Nakamura Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell adhesion and growth Mol Cell Biol 27 5 2007 1889 1903
83. E. Izbicka, J.R. MacDonald, K. Davidson, R.A. Lawrence, L. Gomez, and D.D. Von Hoff 5,6 Dihydro-5'-azacytidine (DHAC) restores androgen responsiveness in androgen-insensitive prostate cancer cells Anticancer Res 19 2A 1999 1285 1291
84. A. Janzer, K. Stamm, A. Becker, A. Zimmer, R. Buettner, and J. Kirfel The H3K4me3 histone demethylase Fbxl10 is a regulator of chemokine expression, cellular morphology, and the metabolome of fibroblasts J Biol Chem 287 37 2012 30984 30992
85. L.R. Jensen, M. Amende, U. Gurok, B. Moser, V. Gimmel, and A. Tzschach Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation Am J Hum Genet 76 2 2005 227 236
86. B. Jin, Q. Tao, J. Peng, H.M. Soo, W. Wu, and J. Ying DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function Hum Mol Genet 17 5 2008 690 709
87. C. Jin, L. Yang, M. Xie, C. Lin, D. Merkurjev, and J.C. Yang Chem-seq permits identification of genomic targets of drugs against androgen receptor regulation selected by functional phenotypic screens Proc Natl Acad Sci U S A 111 25 2014 9235 9240
88. P.A. Jones, and S.M. Taylor Cellular differentiation, cytidine analogs and DNA methylation Cell 20 1 1980 85 93
89. P.A. Jones, S.M. Taylor, T. Mohandas, and L.J. Shapiro Cell cycle-specific reactivation of an inactive X-chromosome locus by 5-azadeoxycytidine Proc Natl Acad Sci U S A 79 4 1982 1215 1219
90. R. Jüttermann, E. Li, and R. Jaenisch Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation Proc Natl Acad Sci U S A 91 25 1994 11797 11801
91. P. Kahl, L. Gullotti, L.C. Heukamp, S. Wolf, N. Friedrichs, and R. Vorreuther Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence Cancer Res 66 23 2006 11341 11347
92. Y. Kanai, S. Ushijima, A.M. Hui, A. Ochiai, H. Tsuda, and M. Sakamoto The E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomas Int J Cancer 71 3 1997 355 359
93. Y. Kanai, S. Ushijima, Y. Nakanishi, M. Sakamoto, and S. Hirohashi Mutation of the DNA methyltransferase (DNMT) 1 gene in human colorectal cancers Cancer Lett 192 1 2003 75 82
94. Y. Kanai, S. Ushijima, A. Ochiai, K. Eguchi, A. Hui, and S. Hirohashi DNA hypermethylation at the D17S5 locus is associated with gastric carcinogenesis Cancer Lett 122 1 1998 135 141
95. Y. Kanai, S. Ushijima, H. Tsuda, M. Sakamoto, and S. Hirohashi Aberrant DNA methylation precedes loss of heterozygosity on chromosome 16 in chronic hepatitis and liver cirrhosis Cancer Lett 148 1 2000 73 80
96. Y. Kanai, S. Ushijima, H. Tsuda, M. Sakamoto, T. Sugimura, and S. Hirohashi Aberrant DNA methylation on chromosome 16 is an early event in hepatocarcinogenesis Cancer Sci 87 12 1996 1210 1217
97. A. Karytinos, F. Forneris, A. Profumo, G. Ciossani, E. Battaglioli, and C. Binda A novel mammalian flavin-dependent histone demethylase J Biol Chem 284 26 2009 17775 17782
98. M. Katoh, and M. Katoh Identification and characterization of JMJD2 family genes in silico Int J Oncol 24 6 2004 1623 1628
99. T.A. Katz, S.N. Vasilatos, E. Harrington, S. Oesterreich, N.E. Davidson, and Y. Huang Inhibition of histone demethylase, LSD2 (KDM1B), attenuates DNA methylation and increases sensitivity to DNMT inhibitor-induced apoptosis in breast cancer cells Breast Cancer Res Treat 146 1 2014 99 108
100. E. Kawakami, A. Tokunaga, M. Ozawa, R. Sakamoto, and N. Yoshida The histone demethylase fbxl11/kdm2a plays an essential role in embryonic development by repressing cell-cycle regulators Mech Dev 135 2014 31 42
101. M. Kawazu, K. Saso, K.I. Tong, T. McQuire, K. Goto, and D. Son Histone demethylase JMJD2B functions as a co-factor of estrogen receptor in breast cancer proliferation and mammary gland development PLoS One 6 3 2011 e17830
102. M.G. Kent-First, M. Maffitt, A. Muallem, P. Brisco, J. Shultz, and S. Ekenberg Gene sequence and evolutionary conservation of human SMCY Nat Genet 14 2 1996 128 129
103. T. Kim, S. Oh, S. Shin, and R. Janknecht Regulation of tumor suppressor p53 and HCT116 cell physiology by histone demethylase JMJD2D/KDM4D PLoS One 7 4 2012 e34618
104. O.N. King, X.S. Li, M. Sakurai, A. Kawamura, N.R. Rose, and S.S. Ng Quantitative high-throughput screening identifies 8-hydroxyquinolines as cell-active histone demethylase inhibitors PLoS One 5 11 2010 e15535
105. C.J. Klein, M. Botuyan, Y. Wu, C.J. Ward, G.A. Nicholson, and S. Hammans Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss Nat Genet 43 6 2011 595 600
106. R.J. Klose, E.M. Kallin, and Y. Zhang JmjC-domain-containing proteins and histone demethylation Nat Rev Genet 7 9 2006 715 727
107. R.J. Klose, K. Yamane, Y. Bae, D. Zhang, H. Erdjument-Bromage, and P. Tempst The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36 Nature 442 7100 2006 312 316
108. R.J. Klose, Q. Yan, Z. Tothova, K. Yamane, H. Erdjument-Bromage, and P. Tempst The retinoblastoma binding protein RBP2 is an H3K4 demethylase Cell 128 5 2007 889 900
109. F. Kottakis, C. Polytarchou, P. Foltopoulou, I. Sanidas, S.C. Kampranis, and P.N. Tsichlis FGF-2 regulates cell proliferation, migration, and angiogenesis through an NDY1/KDM2B-miR-101-EZH2 pathway Mol Cell 43 2 2011 285 298
110. T. Kouzarides Chromatin modifications and their function Cell 128 4 2007 693 705
111. R. Koyama-Nasu, G. David, and N. Tanese The F-box protein Fbl10 is a novel transcriptional repressor of c-Jun Nat Cell Biol 9 9 2007 1074 1080
112. S. Krishnan, and R.C. Trievel Structural and functional analysis of JMJD2D reveals molecular basis for site-specific demethylation among JMJD2 demethylases Structure 21 1 2013 98 108
113. L. Kruidenier, C. Chung, Z. Cheng, J. Liddle, K. Che, and G. Joberty A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response Nature 488 7411 2012 404 408
114. D. Kuck, T. Caulfield, F. Lyko, and J.L. Medina-Franco Nanaomycin A selectively inhibits DNMT3B and reactivates silenced tumor suppressor genes in human cancer cells Mol Cancer Ther 9 11 2010 3015 3023
115. Labelle, M., Boesen, T., Mehrotra, M., Khan, Q., & Ullah, F. (2014). INHIBITORS OF HISTONE DEMETHYLASES: US Patent 20, 140, 371, 195.
116. F. Lan, P.E. Bayliss, J.L. Rinn, J.R. Whetstine, J.K. Wang, and S. Chen A histone H3 lysine 27 demethylase regulates animal posterior development Nature 449 7163 2007 689 694
117. M.G. Lee, J. Norman, A. Shilatifard, and R. Shiekhattar Physical and functional association of a trimethyl H3K4 demethylase and Ring6a/MBLR, a polycomb-like protein Cell 128 5 2007 877 887
118. M.G. Lee, R. Villa, P. Trojer, J. Norman, K. Yan, and D. Reinberg Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination Science 318 5849 2007 447 450
119. M.G. Lee, C. Wynder, N. Cooch, and R. Shiekhattar An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation Nature 437 7057 2005 432 435
120. M.G. Lee, C. Wynder, D.M. Schmidt, D.G. McCafferty, and R. Shiekhattar Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications Chem Biol 13 6 2006 563 567
121. L. Lefebvre, S. Viville, S.C. Barton, F. Ishino, E.B. Keverne, and M.A. Surani Abnormal maternal behaviour and growth retardation associated with loss of the imprinted gene Mest Nat Genet 20 2 1998 163 169
122. H. Lei, S.P. Oh, M. Okano, R. Juttermann, K.A. Goss, and R. Jaenisch De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells Development 122 10 1996 3195 3205
123. H. Leonhardt, A.W. Page, H. Weier, and T.H. Bestor A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei Cell 71 5 1992 865 873
124. T.J. Ley, L. Ding, M.J. Walter, M.D. McLellan, T. Lamprecht, and D.E. Larson DNMT3A mutations in acute myeloid leukemia N Engl J Med 363 25 2010 2424 2433
125. B. Li, M. Zhang, C. Luo, P. Yang, H. Li, and H. Xu Effects of RNA interference-mediated gene silencing of JMJD2A on human breast cancer cell line MDA-MB-231 in vitro J Exp Clin Cancer Res 2011 10.1186/1756-9966-30-90
126. G. Liang, J. He, and Y. Zhang Kdm2b promotes induced pluripotent stem cell generation by facilitating gene activation early in reprogramming Nat Cell Biol 14 5 2012 457 466
127. Y. Liang, D. Quenelle, J.L. Vogel, C. Mascaro, A. Ortega, and T.M. Kristie A novel selective LSD1/KDM1A inhibitor epigenetically blocks herpes simplex virus lytic replication and reactivation from latency MBio 4 1 2013 e512 e558
128. R. Liefke, F. Oswald, C. Alvarado, D. Ferres-Marco, G. Mittler, and P. Rodriguez Histone demethylase KDM5A is an integral part of the core Notch-RBP-J repressor complex Genes Dev 24 6 2010 590 601
129. S. Lim, A. Janzer, A. Becker, A. Zimmer, R. Schüle, and R. Buettner Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology Carcinogenesis 31 3 2010 512 520
130. R. Lin, C. Hsu, and Y. Wang Mithramycin A inhibits DNA methyltransferase and metastasis potential of lung cancer cells Anticancer Drugs 18 10 2007 1157 1164
131. Y. Liu, K. Liu, S. Qin, C. Xu, and J. Min Epigenetic targets and drug discovery: Part 1: Histone methylation Pharmacol Ther 143 3 2014 275 294
132. T. Lu, M.W. Jackson, B. Wang, M. Yang, M.R. Chance, and M. Miyagi Regulation of NF-κB by NSD1/FBXL11-dependent reversible lysine methylation of p65 Proc Natl Acad Sci U S A 107 1 2010 46 51
133. M. Lübbert DNA methylation inhibitors in the treatment of leukemias, myelodysplastic syndromes and hemoglobinopathies: Clinical results and possible mechanisms of action Curr Top Microbiol Immunol 249 2000 135 164
134. X. Luo, Y. Liu, S. Kubicek, J. Myllyharju, A. Tumber, and S. Ng A selective inhibitor and probe of the cellular functions of Jumonji C domain-containing histone demethylases J Am Chem Soc 133 24 2011 9451 9456
135. T. Maes, I. Tirapu, C. Mascaro, A. Ortega, A. Estiarte, and N. Valls Preclinical characterization of a potent and selective inhibitor of the histone demethylase KDM1A for MLL leukemia J Clin Oncol Abstr 31 2013 e13543
136. F.A. Mallette, F. Mattiroli, G. Cui, L.C. Young, M.J. Hendzel, and G. Mer RNF8-and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites EMBO J 31 8 2012 1865 1878
137. R. Margueron, P. Trojer, and D. Reinberg The key to development: Interpreting the histone code? Curr Opin Genet Dev 15 2 2005 163 176
138. J.L. Medina-Franco, F. López-Vallejo, D. Kuck, and F. Lyko Natural products as DNA methyltransferase inhibitors: A computer-aided discovery approach Mol Divers 15 2 2011 293 304
139. E. Metzger, M. Wissmann, N. Yin, J.M. Müller, R. Schneider, and A.H. Peters LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription Nature 437 7057 2005 436 439
140. S. Mimasu, N. Umezawa, S. Sato, T. Higuchi, T. Umehara, and S. Yokoyama Structurally designed trans-2-phenylcyclopropylamine derivatives potently inhibit histone demethylase LSD1/KDM1 Biochemistry 49 30 2010 6494 6503
141. Minucci, S., Mai, A., & Mattevi, A. (2011). Tranylcypromine derivatives as inhibitors of histone demethylases lsd1 and/or lsd2: Google Patents.
142. S. Mizuno, T. Chijiwa, T. Okamura, K. Akashi, Y. Fukumaki, and Y. Niho Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia Blood 97 5 2001 1172 1179
143. H. Mohammad, K. Smitheman, G. van Aller, M. Cusan, S. Kamat, and Y. Liu 212 Novel anti-tumor activity of targeted LSD1 inhibition by GSK2879552 Eur J Cancer 50 2014 72
144. Muñoz, A. O., Laria, J. C., & Fyfe, M. C. T. (2010). Lysine specific demethylase-1 inhibitors and their use: Google Patents.
145. K. Mutze, R. Langer, F. Schumacher, K. Becker, K. Ott, and A. Novotny DNA methyltransferase 1 as a predictive biomarker and potential therapeutic target for chemotherapy in gastric cancer Eur J Cancer 47 12 2011 1817 1825
146. T. Nakamura, T. Mori, S. Tada, W. Krajewski, T. Rozovskaia, and R. Wassell ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation Mol Cell 10 5 2002 1119 1128
147. R. Nathan Inhibition of the histone lysine demethylase JMJD2A by ejection of structural Zn (II) Chem Commun 42 2009 6376 6378
148. H. Ng, and B. Adrian DNA methylation and chromatin modification Curr Opin Genet Dev 9 2 1999 158 163
149. P.A. Northcott, Y. Nakahara, X. Wu, L. Feuk, D.W. Ellison, and S. Croul Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma Nat Genet 41 4 2009 465 472
150. 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 3 1999 247 257
151. S.K. Ooi, C. Qiu, E. Bernstein, K. Li, D. Jia, and Z. Yang DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA Nature 448 7154 2007 714 717
152. M. Orlic, C.E. Spencer, L. Wang, and B.L. Gallie Expression analysis of 6p22 genomic gain in retinoblastoma Genes Chromosomes Cancer 45 1 2006 72 82
153. D.R. Patel, and B.C. Richardson Epigenetic mechanisms in lupus Curr Opin Rheumatol 22 2010 478 482
154. M.T. Pedersen, and K. Helin Histone demethylases in development and disease Trends Cell Biol 20 11 2010 662 671
155. D.F. Peng, Y. Kanai, M. Sawada, S. Ushijima, N. Hiraoka, and T. Kosuge Increased DNA methyltransferase 1 (DNMT1) protein expression in precancerous conditions and ductal carcinomas of the pancreas Cancer Sci 96 7 2005 403 408
156. R. Pfau, A. Tzatsos, S.C. Kampranis, O.B. Serebrennikova, S.E. Bear, and P.N. Tsichlis Members of a family of JmjC domain-containing oncoproteins immortalize embryonic fibroblasts via a JmjC domain-dependent process Proc Natl Acad Sci U S A 105 6 2008 1907 1912
157. R. Plummer, L. Vidal, M. Griffin, M. Lesley, J. de Bono, and S. Coulthard Phase I study of MG98, an oligonucleotide antisense inhibitor of human DNA methyltransferase 1, given as a 7-day infusion in patients with advanced solid tumors Clin Cancer Res 15 9 2009 3177 3183
158. V.K. Ponnaluri, D.T. Vavilala, S. Putty, W.G. Gutheil, and M. Mukherji Identification of non-histone substrates for JMJD2A-C histone demethylases Biochem Biophys Res Commun 390 2 2009 280 284
159. P. Prusevich, J.H. Kalin, S.A. Ming, M. Basso, J. Givens, and X. Li A selective phenelzine analogue inhibitor of histone demethylase LSD1 ACS Chem Biol 9 6 2014 1284 1293
160. L. Qi, F. Zhu, S. Li, L. Si, L. Hu, and H. Tian Retinoblastoma binding protein 2 (RBP2) promotes HIF-1α-VEGF-induced angiogenesis of non-small cell lung cancer via the Akt pathway PLoS One 9 8 2014 e106032
161. A. Razin, and H. Cedar DNA methylation and embryogenesis DNA Methylation, EXS 64 1993 343 357
162. G. Rhyasen Chromatin as a cancer target Oncol Discov 2015 (http://oncologydiscovery.com/2015/01/04/chromatin-as-a-cancer-target-part-ii-chromatin-erasers/)
163. A.F.T. Ribeiro, M. Pratcorona, C. Erpelinck-Verschueren, V. Rockova, M. Sanders, and S. Abbas Mutant DNMT3A: A marker of poor prognosis in acute myeloid leukemia Blood 119 24 2012 5824 5831
164. K.L. Rice, I. Hormaeche, and J.D. Licht Epigenetic regulation of normal and malignant hematopoiesis Oncogene 26 47 2007 6697 6714
165. T. Robak New nucleoside analogs for patients with hematological malignancies Expert Opin Investig Drugs 20 3 2011 343 359
166. K.D. Robertson, E. Uzvolgyi, G. Liang, C. Talmadge, J. Sumegi, and F.A. Gonzales The human DNA methyltransferases (DNMTs) 1, 3a and 3b: Coordinate mRNA expression in normal tissues and overexpression in tumors Nucleic Acids Res 27 11 1999 2291 2298
167. N.R. Rose, S.S. Ng, J. Mecinovic, B.M. Liénard, S.H. Bello, and Z. Sun Inhibitor scaffolds for 2-oxoglutarate-dependent histone lysine demethylases J Med Chem 51 22 2008 7053 7056
168. N.R. Rose, E.C. Woon, G.L. Kingham, O.N. King, J. Mecinovic, and I.J. Clifton Selective inhibitors of the JMJD2 histone demethylases: combined nondenaturing mass spectrometric screening and crystallographic approaches J Med Chem 53 4 2010 1810 1818
169. N.R. Rose, E.C. Woon, A. Tumber, L.J. Walport, R. Chowdhury, and X.S. Li Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases J Med Chem 55 14 2012 6639 6643
170. D. Rotili, and A. Mai Targeting histone demethylases a new avenue for the fight against cancer Genes Cancer 2 6 2011 663 679
171. D. Rotili, S. Tomassi, M. Conte, R. Benedetti, M. Tortorici, and G. Ciossani Pan-histone demethylase inhibitors simultaneously targeting jumonji C and lysine-specific demethylases display high anticancer activities J Med Chem 57 1 2014 42 55
172. L. Rui, N.C. Emre, M.J. Kruhlak, H. Chung, C. Steidl, and G. Slack Cooperative epigenetic modulation by cancer amplicon genes Cancer Cell 18 6 2010 590 605
173. Y. Saito, Y. Kanai, T. Nakagawa, M. Sakamoto, H. Saito, and H. Ishii Increased protein expression of DNA methyltransferase (DNMT) 1 is significantly correlated with the malignant potential and poor prognosis of human hepatocellular carcinomas Int J Cancer 105 4 2003 527 532
174. C. Sakane, T. Okitsu, A. Wada, H. Sagami, and Y. Shidoji Inhibition of lysine-specific demethylase 1 by the acyclic diterpenoid geranylgeranoic acid and its derivatives Biochem Biophys Res Commun 444 1 2014 24 29
175. B.L. Samuels, J. Herndon, D.C. Harmon, R. Carey, J. Aisner, and J.M. Corson Dihydro-5-azacytidine and cisplatin in the treatment of malignant mesothelioma Cancer 82 8 1998 1578 1584
176. D.V. Santi, A. Norment, and C.E. Garrett Covalent bond formation between a DNA-cytosine methyltransferase and DNA containing 5-azacytosine Proc Natl Acad Sci U S A 81 22 1984 6993 6997
177. C. Santos, L. Rodriguez-Revenga, I. Madrigal, C. Badenas, M. Pineda, and M. Milà A novel mutation in JARID1C gene associated with mental retardation Eur J Hum Genet 14 5 2006 583 586
178. L.S. Scheinbart, M.A. Johnson, L.A. Gross, S.R. Edelstein, and B.C. Richardson Procainamide inhibits DNA methyltransferase in a human T cell line J Rheumatol 18 4 1991 530 534
179. T. Schenk, W.C. Chen, S. Göllner, L. Howell, L. Jin, and K. Hebestreit Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia Nat Med 18 4 2012 605 611
180. R. Schiller, G. Scozzafava, A. Tumber, J.R. Wickens, J.T. Bush, and G. Rai A cell-permeable ester derivative of the JmjC histone demethylase inhibitor IOX1 ChemMedChem 9 3 2014 566 571
181. D.M. Schmidt, and D.G. McCafferty trans-2-Phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1 Biochemistry 46 14 2007 4408 4416
182. M.L. Schmitt, A. Hauser, L. Carlino, M. Pippel, J. Schulz-Fincke, and E. Metzger Nonpeptidic propargylamines as inhibitors of lysine specific demethylase 1 (LSD1) with cellular activity J Med Chem 56 18 2013 7334 7342
183. J.H. Schulte, S. Lim, A. Schramm, N. Friedrichs, J. Koster, and R. Versteeg Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy Cancer Res 69 5 2009 2065 2071
184. S.A. Sheardown, S.M. Duthie, C.M. Johnston, A.E. Newall, E.J. Formstone, and R.M. Arkell Stabilization of Xist RNA Mediates Initiation of X Chromosome Inactivation Cell 91 1 1997 99 107
185. H. Shen, L. Wang, M.R. Spitz, W.K. Hong, L. Mao, and Q. Wei A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer Cancer Res 62 17 2002 4992 4995
186. Y. Shi Histone lysine demethylases: Emerging roles in development, physiology and disease Nat Rev Genet 8 11 2007 829 833
187. Y. Shi, F. Lan, C. Matson, P. Mulligan, J.R. Whetstine, and P.A. Cole Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 Cell 119 7 2004 941 953
188. Y. Shi, C. Matson, F. Lan, S. Iwase, T. Baba, and Y. Shi Regulation of LSD1 histone demethylase activity by its associated factors Mol Cell 19 6 2005 857 864
189. S. Shin, and R. Janknecht Diversity within the JMJD2 histone demethylase family Biochem Biophys Res Commun 353 4 2007 973 977
190. V. Singh, P. Sharma, and N. Capalash DNA methyltransferase-1 inhibitors as epigenetic therapy for cancer Curr Cancer Drug Targets 13 4 2013 379 399
191. V. Sorna, E.R. Theisen, B. Stephens, S.L. Warner, D.J. Bearss, and H. Vankayalapati High-throughput virtual screening identifies novel N′-(1-phenylethylidene)-benzohydrazides as potent, specific, and reversible LSD1 inhibitors J Med Chem 56 23 2013 9496 9508
192. P. Srivastava, B.E. Paluch, J. Matsuzaki, S.R. James, G. Collamat-Lai, and J. Karbach Immunomodulatory action of SGI-110, a hypomethylating agent, in acute myeloid leukemia cells and xenografts Leuk Res 38 11 2014 1332 1341
193. B.D. Strahl, and C.D. Allis The language of covalent histone modifications Nature 403 6765 2000 41 45
194. C. Stresemann, B. Brueckner, T. Musch, H. Stopper, and F. Lyko Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines Cancer Res 66 5 2006 2794 2800
195. I. Suetake, F. Shinozaki, J. Miyagawa, H. Takeshima, and S. Tajima DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction J Biol Chem 279 26 2004 27816 27823
196. T. Suzuki, K.I. Minehata, K. Akagi, N.A. Jenkins, and N.G. Copeland Tumor suppressor gene identification using retroviral insertional mutagenesis in Blm-deficient mice EMBO J 25 14 2006 3422 3431
197. T. Suzuki, H. Ozasa, Y. Itoh, P. Zhan, H. Sawada, and K. Mino Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity J Med Chem 56 18 2013 7222 7231
198. L.M. Szewczuk, J.C. Culhane, M. Yang, A. Majumdar, H. Yu, and P.A. Cole Mechanistic analysis of a suicide inactivator of histone demethylase LSD1 Biochemistry 46 23 2007 6892 6902
199. M. Tahiliani, P. Mei, R. Fang, T. Leonor, M. Rutenberg, and F. Shimizu The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation Nature 447 7144 2007 601 605
200. K. Tan, A.L. Shaw, B. Madsen, K. Jensen, J. Taylor-Papadimitriou, and P.S. Freemont Human PLU-1 has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9 J Biol Chem 278 23 2003 20507 20513
201. Y. Tanaka, K. Okamoto, K. Teye, T. Umata, N. Yamagiwa, and Y. Suto JmjC enzyme KDM2A is a regulator of rRNA transcription in response to starvation EMBO J 29 9 2010 1510 1522
202. C.S. Tellez, M.J. Grimes, M.A. Picchi, Y. Liu, T.H. March, and M.D. Reed SGI-110 and entinostat therapy reduces lung tumor burden and reprograms the epigenome Int J Cancer 135 9 2014 2223 2231
203. J.V. Thottassery, V. Sambandam, P.W. Allan, J.A. Maddry, Y.Y. Maxuitenko, and K. Tiwari Novel DNA methyltransferase-1 (DNMT1) depleting anticancer nucleosides, 4′-thio-2′-deoxycytidine and 5-aza-4′-thio-2′-deoxycytidine Cancer Chemother Pharmacol 74 2 2014 291 302
204. Thottassery, J., Tiwari, K. N., Parker, W. B., & Secrist III, J. A. (2010). Use of 2'-deoxy-4'-thiocytidine and its analogues as dna hypomethylating anticancer agents: Google Patents.
205. G. Toyokawa, H. Cho, Y. Iwai, M. Yoshimatsu, M. Takawa, and S. Hayami The histone demethylase JMJD2B plays an essential role in human carcinogenesis through positive regulation of cyclin-dependent kinase 6 Cancer Prev Res 4 12 2011 2051 2061
206. Y. Tsukada, J. Fang, H. Erdjument-Bromage, M.E. Warren, C.H. Borchers, and P. Tempst Histone demethylation by a family of JmjC domain-containing proteins Nature 439 7078 2005 811 816
207. A. Tzatsos, P. Paskaleva, F. Ferrari, V. Deshpande, S. Stoykova, and G. Contino KDM2B promotes pancreatic cancer via polycomb-dependent and-independent transcriptional programs J Clin Invest 123 2 2013 727 739
208. A. Tzatsos, R. Pfau, S.C. Kampranis, and P.N. Tsichlis Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus Proc Natl Acad Sci U S A 106 8 2009 2641 2646
209. A. Tzschach, S. Lenzner, B. Moser, R. Reinhardt, J. Chelly, and J.P. Fryns Novel JARID1C/SMCX mutations in patients with X-linked mental retardation Hum Mutat 27 4 2006 389
210. R. Ueda, T. Suzuki, K. Mino, H. Tsumoto, H. Nakagawa, and Hasegawa Identification of cell-active lysine specific demethylase 1-selective inhibitors J Am Chem Soc 131 48 2009 17536 17537
211. Vakayalapati, H., Soma, V., Warner, S. L., Stephens, B., Bearss, D. J., & Sharma, S. (2012). Substituted (e)-n'-(1-phenylethylidene) benzohydrazide analogs as histone demethylase inhibitors: Google Patents.
212. G. van Haaften, G.L. Dalgliesh, H. Davies, L. Chen, G. Bignell, and C. Greenman Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer Nat Genet 41 5 2009 521 523
213. C. van Oevelen, J. Wang, P. Asp, Q. Yan, W.G. Kaelin Jr., and Y. Kluger A role for mammalian Sin3 in permanent gene silencing Mol Cell 32 3 2008 359 370
214. K.W. Wagner, H. Alam, S.S. Dhar, U. Giri, N. Li, and Y. Wei KDM2A promotes lung tumorigenesis by epigenetically enhancing ERK1/2 signaling J Clin Invest 123 12 2013 5231 5246
215. L.J. Walport, R.J. Hopkinson, M. Vollmar, S.K. Madden, C. Gileadi, and U. Oppermann Human UTY (KDM6C) is a male-specific N-methyl lysyl-demethylase J Biol Chem 289 2014 18302 18313
216. M.J. Walter, L. Ding, D. Shen, J. Shao, M. Grillot, and M. McLellan Recurrent DNMT3A mutations in patients with myelodysplastic syndromes Leukemia 25 7 2011 1153 1158
217. L. Wang, J. Chang, D. Varghese, M. Dellinger, S. Kumar, and A.M. Best A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth Nat Commun 4 2013 2035 10.1038/ncomms3035
218. J. Wang, S. Hevi, J.K. Kurash, H. Lei, F. Gay, and J. Bajko The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation Nat Genet 41 1 2008 125 129
219. L. Wang, J. Wang, S. Sun, M. Rodriguez, P. Yue, and S.J. Jang A novel DNMT3B subfamily, DeltaDNMT3B, is the predominant form of DNMT3B in non-small cell lung cancer Int J Oncol 29 1 2006 201 207
220. Y. Wang, H. Zhang, Y. Chen, Y. Sun, F. Yang, and W. Yu LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer Cell 138 4 2009 660 672
221. J.R. Whetstine, A. Nottke, F. Lan, M. Huarte, S. Smolikov, and Z. Chen Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases Cell 125 3 2006 467 481
222. R.J. Wierda, S.B. Geutskens, J.W. Jukema, P.H. Quax, and P.J. van den Elsen Epigenetics in atherosclerosis and inflammation J Cell Mol Med 14 6a 2010 1225 1240
223. C. Wijmenga, R.S. Hansen, G. Gimelli, E.J. Bjoerck, E.G. Davies, and D. Valentine Genetic variation in ICF syndrome: Evidence for genetic heterogeneity Hum Mutat 16 6 2000 509 517
224. S.K. Williamson, J.J. Crowley, R.B. Livingston, T.J. Panella, and J.W. Goodwin Phase II trial and cost analysis of fazarabine in advanced non-small cell carcinoma of the lung: A Southwest Oncology Group study Invest New Drugs 13 1 1995 67 71
225. J. Winkelmann, L. Lin, B. Schormair, B.R. Kornum, J. Faraco, and G. Plazzi Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy Hum Mol Genet 21 10 2012 2205 2210
226. E.C. Woon, A. Tumber, A. Kawamura, L. Hillringhaus, W. Ge, and N.R. Rose Linking of 2-oxoglutarate and substrate binding sites enables potent and highly selective inhibition of JmjC histone demethylases Angew Chem Int Ed Engl 51 7 2012 1631 1634
227. J. Wu, E.C. Salido, P.H. Yen, T.K. Mohandas, H.H. Heng, and L. Tsui The murine Xe169 gene escapes X-inactivation like its human homologue Nat Genet 7 4 1994 491 496
228. Q. Xie, Y. Bai, J. Wu, Y. Sun, Y. Wang, and Y. Zhang Methylation-mediated regulation of E2F1 in DNA damage-induced cell death J Recept Signal Transduct Res 31 2 2011 139 146
229. S. Yamamoto, Z. Wu, H.G. Russnes, S. Takagi, G. Peluffo, and C. Vaske JARID1B is a luminal lineage-driving oncogene in breast cancer Cancer Cell 25 6 2014 762 777
230. X. Yan, J. Xu, Z. Gu, C. Pan, G. Lu, and Y. Shen Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia Nat Genet 43 4 2011 309 315
231. M. Yang, J.C. Culhane, L.M. Szewczuk, P. Jalili, H.L. Ball, and M. Machius Structural basis for the inhibition of the LSD1 histone demethylase by the antidepressant trans-2-phenylcyclopropylamine Biochemistry 46 27 2007 8058 8065
232. X. Ye, Y. Zheng, Y. Duan, M. Wang, B. Yu, and J. Ren Synthesis and biological evaluation of coumarin-1, 2, 3-triazole-dithiocarbamate hybrids as potent LSD1 inhibitors MedChemComm 5 5 2014 650 654
233. C.B. Yoo, S. Jeong, G. Egger, G. Liang, P. Phiasivongsa, and C. Tang Delivery of 5-aza-2′-deoxycytidine to cells using oligodeoxynucleotides Cancer Res 67 13 2007 6400 6408
234. J. Zeng, Z. Ge, L. Wang, Q. Li, N. Wang, and M. Björkholm The histone demethylase RBP2 Is overexpressed in gastric cancer and its inhibition triggers senescence of cancer cells Gastroenterology 138 3 2010 981 992
235. J. Zhang, J. Baran, A. Cros, J.M. Guberman, S. Haider, and J. Hsu International cancer genome consortium data portal - a one-stop shop for cancer genomics data Database 2011 10.1093/database/bar026
236. Y. Zhang, and D. Reinberg Transcription regulation by histone methylation: Interplay between different covalent modifications of the core histone tails Genes Dev 15 18 2001 2343 2360
237. Y. Zheng, Y. Duan, J. Ma, R. Xu, X. Zi, and W. Lv Triazole-dithiocarbamate based selective lysine specific demethylase 1 (LSD1) inactivators inhibit gastric cancer cell growth, invasion, and migration J Med Chem 56 21 2013 8543 8560
238. L. Zhou, X. Cheng, B.A. Connolly, M.J. Dickman, P.J. Hurd, and D.P. Hornby Zebularine: A novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases J Mol Biol 321 4 2002 591 599
239. M.R. Zou, J. Cao, Z. Liu, S.J. Huh, K. Polyak, and Q. Yan Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes J Biol Chem 289 2014 17620 17633