Erasing the methyl mark: Histone demethylases at the center of cellular differentiation and disease

Genes and Development

Volumn 22, Issue 9, 2008, Pages 1115-1140

  Cloos, Paul A C ^a   Christensen, Jesper ^a   Agger, Karl ^a   Helin, Kristian ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Cancer; Demethylases; Differentiation; Epigenetic; Histone; JmjC

Indexed keywords

AMINE OXIDASE (FLAVIN CONTAINING); ARGININE; CELL NUCLEUS RECEPTOR; HISTONE; LYSINE; METHYLTRANSFERASE;

BIOCHEMISTRY; BIOLOGY; CELL AGING; CELL DIFFERENTIATION; CELL MATURATION; DEMETHYLATION; EMBRYO; FEMALE; GENOMIC INSTABILITY; HUMAN; NEOPLASM; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FAMILY; REVIEW; X CHROMOSOME INACTIVATION;

AGING; ANIMALS; CELL DIFFERENTIATION; HISTONES; HUMANS; METHYLATION; MODELS, BIOLOGICAL; NEOPLASMS; OXIDOREDUCTASES, N-DEMETHYLATING; PHYLOGENY;

EID: 43249102851     PISSN: 08909369     EISSN: 15495477     Source Type: Journal    
DOI: 10.1101/gad.1652908     Document Type: Review

References (177)

1. Agger, K., Cloos, P.A., Christensen, J., Pasini, D., Rose, S., Rappsilber, J., Issaeva, I., Canaani, E., Salcini, A.E., and Helin, K. 2007. UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature 449: 731-734.
2. Ahmed, S., Palermo, C., Wan, S., and Walworth, N.C. 2004. A novel protein with similarities to Rb binding protein 2 compensates for loss of Chk1 function and affects histone modification in fission yeast. Mol. Cell. Biol. 24: 3660-3669.
3. Akasaka, T., Takahashi, N., Suzuki, M., Koseki, H., Bodmer, R., and Koga, H. 2002. MBLR, a new RING finger protein resembling mammalian Polycomb gene products, is regulated by cell cycle-dependent phosphorylation. Genes Cells 7: 835-850.
4. Allis, C.D., Berger, S.L., Cote, J., Dent, S., Jenuwien, T., Kouzarides, T., Pillus, L., Reinberg, D., Shi, Y., Shiekhattar, R., et al. 2007. New nomenclature for chromatin-modifying enzymes. Cell 131: 633-636.
5. Bannister, A.J., Zegerman, P., Partridge, J.F., Miska, E.A., Thomas, J.O., Allshire, R.C., and Kouzarides, T. 2001. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410: 120-124.
6. Bannister, A.J., Schneider, R., and Kouzarides, T. 2002. Histone methylation: Dynamic or static? Cell 109: 801-806.
7. Barrett, A., Madsen, B., Copier, J., Lu, P.J., Cooper, L., Scibetta, A.G., Burchell, J., and Taylor-Papadimitriou, J. 2002. PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: A new cancer/testis antigen? Int. J. Cancer 101: 581-588.
8. Bauer, U.M., Daujat, S., Nielsen, S.J., Nightingale, K., and Kouzarides, T. 2002. Methylation at arginine 17 of histone H3 is linked to gene activation. EMBO Rep. 3: 39-44.
9. Beaudoin III, G.M., Sisk, J.M., Coulombe, P.A., and Thompson, C.C. 2005. Hairless triggers reactivation of hair growth by promoting Wnt signaling. Proc. Natl. Acad. Sci. 102: 14653-14658.
10. Benevolenskaya, E.V., Murray, H.L., Branton, P., Young, R.A., and Kaelin Jr., W.G. 2005. Binding of pRB to the PHD protein RBP2 promotes cellular differentiation. Mol. Cell 18: 623-635.
11. Berger, S.L. 2007. The complex language of chromatin regulation during transcription. Nature 447: 407-412.
12. Bernstein, B.E., Kamal, M., Lindblad-Toh, K., Bekiranov, S., Bailey, D.K., Huebert, D.J., McMahon, S., Karlsson, E.K., Kulbokas III, E.J., Gingeras, T.R., et al. 2005. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120: 169-181.
13. Bernstein, B.E., Mikkelsen, T.S., Xie, X., Kamal, M., Huebert, D.J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. 2006. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125: 315-326.
14. Blair, I.P., Dawkins, J.L., and Nicholson, G.A. 1997. Fine mapping of the hereditary sensory neuropathy type I locus on chromosome 9q22.1 → q22.3: Exclusion of GAS1 and XPA. Cytogenet. Cell Genet. 78: 140-144.
15. Blatch, G.L. and Lassle, M. 1999. The tetratricopeptide repeat: A structural motif mediating protein-protein interactions. Bioessays 21: 932-939.
16. Bodmer, D., Schepens, M., Eleveld, M.J., Schoenmakers, E.F., and Geurts van Kessel, A. 2003. Disruption of a novel gene, DIRC3, and expression of DIRC3-HSPBAP1 fusion transcripts in a case of familial renal cell cancer and t(2;3)(q35;q21). Genes Chromosomes Cancer 38: 107-116.
17. Bose, J., Gruber, A.D., Helming, L., Schiebe, S., Wegener, I., Hafner, M., Beales, M., Kontgen, F., and Lengeling, A. 2004. The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal. J. Biol. 3: 15. doi: 10.1186/jbiol10.
18. Boyer, L.A., Plath, K., Zeitlinger, J., Brambrink, T., Medeiros, L.A., Lee, T.I., Levine, S.S., Wernig, M., Tajonar, A., Ray, M.K., et al. 2006. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441: 349-353.
19. Bracken, A.P., Dietrich, N., Pasini, D., Hansen, K.H., and Helin, K. 2006. Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes & Dev. 20: 1123-1136.
20. Bracken, A.P., Kleine-Kohlbrecher, D., Dietrich, N., Pasini, D., Gargiulo, G., Beekman, C., Theilgaard-Monch, K., Minucci, S., Porse, B.T., Marine, J.C., et al. 2007. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes & Dev. 21: 525-530.
21. Braig, M., Lee, S., Loddenkemper, C., Rudolph, C., Peters, A.H., Schlegelberger, B., Stein, H., Dorken, B., Jenuwein, T., and Schmitt, C.A. 2005. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436: 660-665.
22. Brown, C.J., Miller, A.P., Carrel, L., Rupert, J.L., Davies, K.E., and Willard, H.F. 1995. The DXS423E gene in Xp11.21 escapes X chromosome inactivation. Hum. Mol. Genet. 4: 251-255.
23. Carrozza, M.J., Li, B., Florens, L., Suganum, T., Swanson, S.K., Lee, K.K., Shia, W.J., Anderson, S., Yates, J., Washburn, M.P., et al. 2005. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell 123: 581-592.
24. Castermans, D., Vermeesch, J.R., Fryns, J.P., Steyaert, J.G., Van de Ven, W.J., Creemers, J.W., and Devriendt, K. 2007. Identification and characterization of the TRIP8 and REEP3 genes on chromosome 10q21.3 as novel candidate genes for autism. Eur. J. Hum. Genet. 15: 422-431.
25. Chan, S.W. and Hong, W. 2001. Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription. J. Biol. Chem. 276: 28402-28412.
26. Chang, B., Chen, Y., Zhao, Y., and Bruick, R.K. 2007. JMJD6 is a histone arginine demethylase. Science 318: 444-447.
27. Chen, Y.T. and Old, L.J. 1999. Cancer-testis antigens: Targets for cancer immunotherapy. Cancer J. Sci. Am. 5: 16-17.
28. Chen, Z., Zang, J., Kappler, J., Hong, X., Crawford, F., Wang, Q., Lan, F., Jiang, C., Whetstine, J., Dai, S., et al. 2007. Structural basis of the recognition of a methylated histone tail by JMJD2A. Proc. Natl. Acad. Sci. 104: 10818-10823.
29. Chinenov, Y. 2002. A second catalytic domain in the Elp3 histone acetyltransferases: A candidate for histone demethylase activity? Trends Biochem. Sci. 27: 115-117.
30. Cho, Y.W., Hong, T., Hong, S., Guo, H., Yu, H., Kim, D., Guszczynski, T., Dressler, G.R., Copeland, T.D., Kalkum, M., et al. 2007. PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex. J. Biol. Chem. 282: 20395-20406.
31. Chosed, R. and Dent, S.Y. 2007. A two-way street: LSD1 regulates chromatin boundary formation in S. pombe and Drosophila. Mol. Cell 26: 160-162.
32. Christensen, J., Agger, K., Cloos, P.A., Pasini, D., Rose, S., Sennels, L., Rappsilber, J., Hansen, K.H., Salcini, A.E., and Helin, K. 2007. RBP2 belongs to a family of demethylases, specific for tri- and dimethylated lysine 4 on histone 3. Cell 128: 1063-1076.
33. Cloos, P.A. and Christgau, S. 2004. Post-translational modifications of proteins: Implications for aging, antigen recognition, and autoimmunity. Biogerontology 5: 139-158.
34. Cloos, P.A., Christensen, J., Agger, K., Maiolica, A., Rappsilber, J., Antal, T., Hansen, K.H., and Helin, K. 2006. The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3. Nature 442: 307-311.
35. Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A.J., Barradas, M., Benguria, A., Zaballos, A., Flores, J.M., Barbacid, M., et al. 2005. Tumour biology: Senescence in pre-malignant tumours. Nature 436: 642.
36. Couture, J.F., Collazo, E., Ortiz-Tello, P.A., Brunzelle, J.S., and Trievel, R.C. 2007. Specificity and mechanism of JMJD2A, a trimethyllysine- specific histone demethylase. Nat. Struct. Mol. Biol. 14: 689-695.
37. Culhane, J.C., Szewczuk, L.M., Liu, X., Da, G., Marmorstein, R., and Cole, P.A. 2006. A mechanism-based inactivator for histone demethylase LSD1. J. Am. Chem. Soc. 128: 4536-4537.
38. Cuthbert, G.L., Daujat, S., Snowden, A.W., Erdjument-Bromage, H., Hagiwara, T., Yamada, M., Schneider, R., Gregory, P.D., Tempst, P., Bannister, A.J., et al. 2004. Histone deimination antagonizes arginine methylation. Cell 118: 545-553.
39. D'Andrea, L.D. and Regan, L. 2003. TPR proteins: The versatile helix. Trends Biochem. Sci. 28: 655-662.
40. Defeo-Jones, D., Huang, P.S., Jones, R.E., Haskell, K.M., Vuocolo, G.A., Hanobik, M.G., Huber, H.E., and Oliff, A. 1991. Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product. Nature 352: 251-254.
41. DeSanta, F., Totaro, M.G., Prosperini, E., Notarbartolo, S., Testa, G., and Natoli, G. 2007. The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing. Cell 130: 1083-1094.
42. Di Stefano, L., Ji, J.Y., Moon, N.S., Herr, A., and Dyson, N. 2007. Mutation of Drosophila Lsd1 disrupts H3-K4 methylation, resulting in tissue-specific defects during development. Curr. Biol. 17: 808-812.
43. Dodd, I.B., Micheelsen, M.A., Sneppen, K., and Thon, G. 2007. Theoretical analysis of epigenetic cell memory by nucleosome modification. Cell 129: 813-822.
44. Falnes, P.O., Johansen, R.F., and Seeberg, E. 2002. AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature 419: 178-182.
45. Fattaey, A.R., Helin, K., Dembski, M.S., Dyson, N., Harlow, E., Vuocolo, G.A., Hanobik, M.G., Haskell, K.M., Oliff, A., Defeo-Jones, D., et al. 1993. Characterization of the retinoblastoma binding proteins RBP1 and RBP2. Oncogene 8: 3149-3156.
46. Fodor, B.D., Kubicek, S., Yonezawa, M., O'Sullivan, R.J., Sengupta, R., Perez-Burgos, L., Opravil, S., Mechtler, K., Schotta, G., and Jenuwein, T. 2006. Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cells. Genes & Dev. 20: 1557-1562.
47. Forneris, F., Binda, C., Vanoni, M.A., Battaglioli, E., and Mattevi, A. 2005. Human histone demethylase LSD1 reads the histone code. J. Biol. Chem. 280: 41360-41365.
48. Forneris, F., Binda, C., Dall'Aglio, A., Fraaije, M.W., Battaglioli, E., and Mattevi, A. 2006. A highly specific mechanism of histone H3-K4 recognition by histone demethylase LSD1. J. Biol. Chem. 281: 35289-35295.
49. Frescas, D., Guardavaccaro, D., Bassermann, F., Koyama-Nasu, R., and Pagano, M. 2007. JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes. Nature 450: 309-313.
50. Garcia-Bassets, I., Kwon, Y.S., Telese, F., Prefontaine, G.G., Hutt, K.R., Cheng, C.S., Ju, B.G., Ohgi, K.A., Wang, J., Escoubet-Lozach, L., et al. 2007. Histone methylation-dependent mechanisms impose ligand dependency for gene activation by nuclear receptors. Cell 128: 505-518.
51. Gearhart, M.D., Corcoran, C.M., Wamstad, J.A., and Bardwell, V.J. 2006. Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets. Mol. Cell. Biol. 26: 6880-6889.
52. Gerken, T., Girard, C.A., Tung, Y.C., Webby, C.J., Saudek, V., Hewitson, K.S., Yeo, G.S., McDonough, M.A., Cunliffe, S., McNeill, L.A., et al. 2007. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318: 1469-1472.
53. Gildea, J.J., Lopez, R., and Shearn, A. 2000. A screen for new trithorax group genes identified little imaginal discs, the Drosophila melanogaster homologue of human retinoblastoma binding protein 2. Genetics 156: 645-663.
54. Goudie, D.R., Yuille, M.A., Leversha, M.A., Furlong, R.A., Carter, N.P., Lush, M.J., Affara, N.A., and Ferguson-Smith, M.A. 1993. Multiple self-healing squamous epitheliomata (ESS1) mapped to chromosome 9q22-q31 in families with common ancestry. Nat. Genet. 3: 165-169.
55. Gray, S.G., Iglesias, A.H., Lizcano, F., Villanueva, R., Camelo, S., Jingu, H., Teh, B.T., Koibuchi, N., Chin, W.W., Kokkotou, E., et al. 2005. Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein. J. Biol. Chem. 280: 28507-28518.
56. Greenfield, A., Carrel, L., Pennisi, D., Philippe, C., Quaderi, N., Siggers, P., Steiner, K., Tam, P.P., Monaco, A.P., Willard, H.F., et al. 1998. The UTX gene escapes X inactivation in mice and humans. Hum. Mol. Genet. 7: 737-742.
57. Guccione, E., Bassi, C., Casadio, F., Martinato, F., Cesaroni, M., Schuchlautz, H., Luscher, B., and Amati, B. 2007. Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive. Nature 449: 933-937.
58. Heard, E. 2005. Delving into the diversity of facultative heterochromatin: The epigenetics of the inactive X chromosome. Curr. Opin. Genet. Dev. 15: 482-489.
59. Heard, E., Rougeulle, C., Arnaud, D., Avner, P., Allis, C.D., and Spector, D.L. 2001. Methylation of histone H3 at Lys-9 is an early mark on the X chromosome during X inactivation. Cell 107: 727-738.
60. Heery, D.M., Kalkhoven, E., Hoare, S., and Parker, M.G. 1997. A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature 387: 733-736.
61. Hong, S., Cho, Y.W., Yu, L.R., Yu, H., Veenstra, T.D., and Ge, K. 2007. Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases. Proc. Natl. Acad. Sci. 104: 18439-18444.
62. Hoog, C., Schalling, M., Grunder-Brundell, E., and Daneholt, B. 1991. Analysis of a murine male germ cell-specific transcript that encodes a putative zinc finger protein. Mol. Reprod. Dev. 30: 173-181.
63. Hu, Z., Gomes, I., Horrigan, S.K., Kravarusic, J., Mar, B., Arbieva, Z., Chyna, B., Fulton, N., Edassery, S., Raza, A., et al. 2001. A novel nuclear protein, 5qNCA (LOC51780) is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31. Oncogene 20: 6946-6954.
64. Huang, Y., Fang, J., Bedford, M.T., Zhang, Y., and Xu, R.M. 2006. Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A. Science 312: 748-751.
65. Huang, J., Sengupta, R., Espejo, A.B., Lee, M.G., Dorsey, J.A., Richter, M., Opravil, S., Shiekhattar, R., Bedford, M.T., Jenuwein, T., et al. 2007. p53 is regulated by the lysine demethylase LSD1. Nature 449: 105-108.
66. Huang, Y., Greene, E., Murray Stewart, T., Goodwin, A.C., Baylin, S.B., Woster, P.M., and Casero Jr., R.A. 2007. Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes. Proc. Natl. Acad. Sci. 104: 8023-8028.
67. Issaeva, I., Zonis, Y., Rozovskaia, T., Orlovsky, K., Croce, C.M., Nakamura, T., Mazo, A., Eisenbach, L., and Canaani, E. 2007. Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell adhesion and growth. Mol. Cell. Biol. 27: 1889-1903.
68. Iwase, S., Lan, F., Bayliss, P., de la Torre-Ubieta, L., Huarte, M., Qi, H.H., Whetstine, J.R., Bonni, A., Roberts, T.M., and Shi, Y. 2007. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell 128: 1077-1088.
69. Jensen, L.R., Amende, M., Gurok, U., Moser, B., Gimmel, V., Tzschach, A., Janecke, A.R., Tariverdian, G., Chelly, J., Fryns, J.P., et al. 2005. Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation. Am. J. Hum. Genet. 76: 227-236.
70. Jepsen, K., Solum, D., Zhou, T., McEvilly, R.J., Kim, H.J., Glass, C.K., Hermanson, O., and Rosenfeld, M.G. 2007. SMRT-mediated repression of an H3K27 demethylase in progression from neural stem cell to neuron. Nature 450: 415-419.
71. Jiang, M., Ma, Y., Cheng, H., Ni, X., Guo, L., Xie, Y., and Mao, Y. 2001. Molecular cloning and characterization of a novel human gene (HSPBAP1) from human fetal brain. Cytogenet. Cell Genet. 95: 48-51.
72. Joshi, A.A. and Struhl, K. 2005. Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Mol. Cell 20: 971-978.
73. Jung, J., Kim, T.G., Lyons, G.E., Kim, H.R., and Lee, Y. 2005a. Jumonji regulates cardiomyocyte proliferation via interaction with retinoblastoma protein. J. Biol. Chem. 280: 30916-30923.
74. Jung, J., Mysliwiec, M.R., and Lee, Y. 2005b. Roles of JUMONJI in mouse embryonic development. Dev. Dyn. 232: 21-32.
75. Keogh, M.C., Kurdistani, S.K., Morris, S.A., Ahn, S.H., Podolny, V., Collins, S.R., Schuldiner, M., Chin, K., Punna, T., Thompson, N.J., et al. 2005. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell 123: 593-605.
76. Kim, T.G., Chen, J., Sadoshima, J., and Lee, Y. 2004. Jumonji represses atrial natriuretic factor gene expression by inhibiting transcriptional activities of cardiac transcription factors. Mol. Cell. Biol. 24: 10151-10160.
77. Kim, J., Daniel, J., Espejo, A., Lake, A., Krishna, M., Xia, L., Zhang, Y., and Bedford, M.T. 2006. Tudor, MBT and chromo domains gauge the degree of lysine methylation. EMBO Rep. 7: 397-403.
78. Kirmizis, A., Santos-Rosa, H., Penkett, C.J., Singer, M.A., Vermeulen, M., Mann, M., Bahler, J., Green, R.D., and Kouzarides, T. 2007. Arginine methylation at histone H3R2 controls deposition of H3K4 trimethylation. Nature 449: 928-932.
79. Klose, R.J., Kallin, E.M., and Zhang, Y. 2006a. JmjC-domain-containing proteins and histone demethylation. Nat. Rev. Genet. 7: 715-727.
80. Klose, R.J., Yamane, K., Bae, Y., Zhang, D., Erdjument-Bromage, H., Tempst, P., Wong, J., and Zhang, Y. 2006b. The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36. Nature 442: 312-316.
81. Klose, R.J., Yan, Q., Tothova, Z., Yamane, K., Erdjument-Bromage, H., Tempst, P., Gilliland, D.G., Zhang, Y., and Kaelin Jr., W.G. 2007. The retinoblastoma binding protein RBP2 is an H3K4 demethylase. Cell 128: 889-900.
82. Koivisto, A.M., Ala-Mello, S., Lemmela, S., Komu, H.A., Rautio, J., and Jarvela, I. 2007. Screening of mutations in the PHF8 gene and identification of a novel mutation in a Finnish family with XLMR and cleft lip/cleft palate. Clin. Genet. 72: 145-149.
83. Kouzarides, T. 2007. Chromatin modifications and their function. Cell 128: 693-705.
84. Koyama-Nasu, R., David, G., and Tanese, N. 2007. The F-box protein Fbl10 is a novel transcriptional repressor of c-Jun. Nat. Cell Biol. 9: 1074-1080.
85. Lachner, M., O'Carroll, D., Rea, S., Mechtler, K., and Jenuwein, T. 2001. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410: 116-120.
86. Lan, F., Bayliss, P.E., Rinn, J.L., Whetstine, J.R., Wang, J.K., Chen, S., Iwase, S., Alpatov, R., Issaeva, I., Canaani, E., et al. 2007a. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature 449: 689-694.
87. Lan, F., Collins, R.E., De Cegli, R., Alpatov, R., Horton, J.R., Shi, X., Gozani, O., Cheng, X., and Shi, Y. 2007b. Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression. Nature 448: 718-722.
88. Lan, F., Zaratiegui, M., Villen, J., Vaughn, M.W., Verdel, A., Huarte, M., Shi, Y., Gygi, S.P., Moazed, D., and Martienssen, R.A. 2007c. S. pombe LSD1 homologs regulate heterochromatin propagation and euchromatic gene transcription. Mol. Cell 26: 89-101.
89. Lando, D., Peet, D.J., Gorman, J.J., Whelan, D.A., Whitelaw, M.L., and Bruick, R.K. 2002a. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes & Dev. 16: 1466-1471.
90. Lando, D., Peet, D.J., Whelan, D.A., Gorman, J.J., and Whitelaw, M.L. 2002b. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science 295: 858-861.
91. Laumonnier, F., Holbert, S., Ronce, N., Faravelli, F., Lenzner, S., Schwartz, C.E., Lespinasse, J., Van Esch, H., Lacombe, D., Goizet, C., et al. 2005. Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate. J. Med. Genet. 42: 780-786.
92. Lazzerini Denchi, E., Attwooll, C., Pasini, D., and Helin, K. 2005. Deregulated E2F activity induces hyperplasia and senescence-like features in the mouse pituitary gland. Mol. Cell. Biol. 25: 2660-2672.
93. Lee, J.S. and Shilatifard, A. 2007. A site to remember: H3K36 methylation a mark for histone deacetylation. Mutat. Res. 618: 130-134.
94. Lee, Y., Song, A.J., Baker, R., Micales, B., Conway, S.J., and Lyons, G.E. 2000. Jumonji, a nuclear protein that is necessary for normal heart development. Circ. Res. 86: 932-938.
95. Lee, M.G., Wynder, C., Cooch, N., and Shiekhattar, R. 2005. An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature 437: 432-435.
96. Lee, M.G., Wynder, C., Schmidt, D.M., McCafferty, D.G., and Shiekhattar, R. 2006. Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chem. Biol. 13: 563-567.
97. Lee, T.I., Jenner, R.G., Boyer, L.A., Guenther, M.G., Levine, S.S., Kumar, R.M., Chevalier, B., Johnstone, S.E., Cole, M.F., Isono, K., et al. 2006. Control of developmental regulators by polycomb in human embryonic stem cells. Cell 125: 301-313.
98. Lee, M.G., Norman, J., Shilatifard, A., and Shiekhattar, R. 2007a. Physical and functional association of a trimethyl H3K4 demethylase and Ring6a/MBLR, a polycomb-like protein. Cell 128: 877-887.
99. Lee, M.G., Villa, R., Trojer, P., Norman, J., Yan, K.P., Reinberg, D., Croce, L.D., and Shiekhattar, R. 2007b. Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination. Science 318: 447-450.
100. Lee, J., Thompson, J.R., Botuyan, M.V., and Mer, G. 2008. Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor. Nat. Struct. Mol. Biol. 15: 109-111.
101. Li, B., Gogol, M., Carey, M., Pattenden, S.G., Seidel, C., and Workman, J.L. 2007. Infrequently transcribed long genes depend on the Set2/Rpd3S pathway for accurate transcription. Genes & Dev. 21: 1422-1430.
102. Liang, G., Lin, J.C., Wei, V., Yoo, C., Cheng, J.C., Nguyen, C.T., Weisenberger, D.J., Egger, G., Takai, D., Gonzales, F.A., et al. 2004. Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome. Proc. Natl. Acad. Sci. 101: 7357-7362.
103. Liu, C., Gilmont, R.R., Benndorf, R., and Welsh, M.J. 2000. Identification and characterization of a novel protein from Sertoli cells, PASS1, that associates with mammalian small stress protein hsp27. J. Biol. Chem. 275: 18724-18731.
104. Lockman, K., Taylor, J.M., and Mack, C.P. 2007. The histone demethylase, Jmjd1a, interacts with the myocardin factors to regulate SMC differentiation marker gene expression. Circ. Res. 101: e115-e123. doi: 10.1161/CIRCRESAHA.107.164178.
105. Loh, Y.H., Zhang, W., Chen, X., George, J., and Ng, H.H. 2007. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes & Dev. 21: 2545-2557.
106. Lu, P.J., Sundquist, K., Baeckstrom, D., Poulsom, R., Hanby, A., Meier-Ewert, S., Jones, T., Mitchell, M., Pitha-Rowe, P., Freemont, P., et al. 1999. A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer. J. Biol. Chem. 274: 15633-15645.
107. MacLellan, W.R., Garcia, A., Oh, H., Frenkel, P., Jordan, M.C., Roos, K.P., and Schneider, M.D. 2005. Overlapping roles of pocket proteins in the myocardium are unmasked by germ line deletion of p130 plus heart-specific deletion of Rb. Mol. Cell. Biol. 25: 2486-2497.
108. Metivier, R., Penot, G., Hubner, M.R., Reid, G., Brand, H., Kos, M., and Gannon, F. 2003. Estrogen receptor-α directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115: 751-763.
109. Metzger, E., Wissmann, M., Yin, N., Muller, J.M., Schneider, R., Peters, A.H., Gunther, T., Buettner, R., and Schule, R. 2005. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 437: 436-439.
110. Michaloglou, C., Vredeveld, L.C., Soengas, M.S., Denoyelle, C., Kuilman, T., van der Horst, C.M., Majoor, D.M., Shay, J.W., Mooi, W.J., and Peeper, D.S. 2005. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436: 720-724.
111. Nakashima, K., Hagiwara, T., and Yamada, M. 2002. Nuclear localization of peptidylarginine deiminase V and histone deimination in granulocytes. J. Biol. Chem. 277: 49562-49568.
112. Narita, M., Nunez, S., Heard, E., Lin, A.W., Hearn, S.A., Spector, D.L., Hannon, G.J., and Lowe, S.W. 2003. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113: 703-716.
113. Ng, S.S., Kavanagh, K.L., McDonough, M.A., Butler, D., Pilka, E.S., Lienard, B.M., Bray, J.E., Savitsky, P., Gileadi, O., von Delft, F., et al. 2007. Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity. Nature 448: 87-91.
114. Nicholson, G.A., Dawkins, J.L., Blair, I.P., Kennerson, M.L., Gordon, M.J., Cherryson, A.K., Nash, J., and Bananis, T. 1996. The gene for hereditary sensory neuropathy type I (HSN-I) maps to chromosome 9q22.1-q22.3. Nat. Genet. 13: 101-104.
115. Nicolas, E., Lee, M.G., Hakimi, M.A., Cam, H.P., Grewal, S.I., and Shiekhattar, R. 2006. Fission yeast homologs of human histone H3 lysine 4 demethylase regulate a common set of genes with diverse functions. J. Biol. Chem. 281: 35983-35988.
116. Nigro, J.M., Baker, S.J., Preisinger, A.C., Jessup, J.M., Hostetter, R., Cleary, K., Bigner, S.H., Davidson, N., Baylin, S., Devilee, P., et al. 1989. Mutations in the p53 gene occur in diverse human tumour types. Nature 342: 705-708.
117. Noma, K., Allis, C.D., and Grewal, S.I. 2001. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science 293: 1150-1155.
118. Ogawa, H., Ishiguro, K., Gaubatz, S., Livingston, D.M., and Nakatani, Y. 2002. A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. Science 296: 1132-1136.
119. Okada, Y., Scott, G., Ray, M.K., Mishina, Y., and Zhang, Y. 2007. Histone demethylase JHDM2A is critical for Tnp1 and Prm1 transcription and spermatogenesis. Nature 450: 119-123.
120. Okamoto, I., Otte, A.P., Allis, C.D., Reinberg, D., and Heard, E. 2004. Epigenetic dynamics of imprinted X inactivation during early mouse development. Science 303: 644-649.
121. Panteleyev, A.A., Botchkareva, N.V., Sundberg, J.P., Christiano, A.M., and Paus, R. 1999. The role of the hairless (hr) gene in the regulation of hair follicle catagen transformation. Am. J. Pathol. 155: 159-171.
122. Pasini, D., Hansen, K.H., Christensen, J., Agger, K., Cloos, P.A.C., and Helin, K. 2008. Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-Repressive Complex 2. Genes & Dev. (in press) doi: 10.1101/gad.470008.
123. Patel, S.R., Kim, D., Levitan, I., and Dressler, G.R. 2007. The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex. Dev. Cell 13: 580-592.
124. Pavri, R., Zhu, B., Li, G., Trojer, P., Mandal, S., Shilatifard, A., and Reinberg, D. 2006. Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell 125: 703-717.
125. Pedrosa, E., Ye, K., Nolan, K.A., Morrell, L., Okun, J.M., Persky, A.D., Saito, T., and Lachman, H.M. 2007. Positive association of schizophrenia to JARID2 gene. Am. J. Med. Genet. B Neuropsychiatr. Genet. 144: 45-51.
126. Peters, A.H., O'Carroll, D., Scherthan, H., Mechtler, K., Sauer, S., Schofer, C., Weipoltshammer, K., Pagani, M., Lachner, M., Kohlmaier, A., et al. 2001. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107: 323-337.
127. Pothof, J., van Haaften, G., Thijssen, K., Kamath, R.S., Fraser, A.G., Ahringer, J., Plasterk, R.H., and Tijsterman, M. 2003. Identification of genes that protect the C. elegans genome against mutations by genome-wide RNAi. Genes & Dev. 17: 443-448.
128. Potter, G.B., Beaudoin III, G.M., DeRenzo, C.L., Zarach, J.M., Chen, S.H., and Thompson, C.C. 2001. The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor. Genes & Dev. 15: 2687-2701.
129. Potter, G.B., Zarach, J.M., Sisk, J.M., and Thompson, C.C. 2002. The thyroid hormone-regulated corepressor hairless associates with histone deacetylases in neonatal rat brain. Mol. Endocrinol. 16: 2547-2560.
130. Reik, W. 2007. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447: 425-432.
131. Rosenfeld, M.G., Lunyak, V.V., and Glass, C.K. 2006. Sensors and signals: A coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response. Genes & Dev. 20: 1405-1428.
132. Rudolph, T., Yonezawa, M., Lein, S., Heidrich, K., Kubicek, S., Schafer, C., Phalke, S., Walther, M., Schmidt, A., Jenuwein, T., et al. 2007. Heterochromatin formation in Drosophila is initiated through active removal of H3K4 methylation by the LSD1 homolog SU(VAR)3-3. Mol. Cell 26: 103-115.
133. Sanchez, C., Sanchez, I., Demmers, J.A., Rodriguez, P., Strouboulis, J., and Vidal, M. 2007. Proteomics analysis of Ring1B/Rnf2 interactors identifies a novel complex with the Fbxl10/Jhdm1B histone demethylase and the Bcl6 interacting corepressor. Mol. Cell. Proteomics 6: 820-834.
134. Santos, C., Rodriguez-Revenga, L., Madrigal, I., Badenas, C., Pineda, M., and Mila, M. 2006. A novel mutation in JARID1C gene associated with mental retardation. Eur. J. Hum. Genet. 14: 583-586.
135. Santos-Rosa, H., Schneider, R., Bannister, A.J., Sherriff, J., Bernstein, B.E., Emre, N.C., Schreiber, S.L., Mellor, J., and Kouzarides, T. 2002. Active genes are tri-methylated at K4 of histone H3. Nature 419: 407-411.
136. Sarmento, O.F., Digilio, L.C., Wang, Y., Perlin, J., Herr, J.C., Allis, C.D., and Coonrod, S.A. 2004. Dynamic alterations of specific histone modifications during early murine development. J. Cell Sci. 117: 4449-4459.
137. Schneider, J.E., Bose, J., Bamforth, S.D., Gruber, A.D., Broadbent, C., Clarke, K., Neubauer, S., Lengeling, A., and Bhattacharya, S. 2004. Identification of cardiac malformations in mice lacking Ptdsr using a novel high-throughput magnetic resonance imaging technique. BMC Dev. Biol. 4: 16. doi: 10.1186/1471-213X-4-16.
138. Schneider, R., Bannister, A.J., Myers, F.A., Thorne, A.W., Crane-Robinson, C., and Kouzarides, T. 2004. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat. Cell Biol. 6: 73-77.
139. Secombe, J. and Eisenman, R.N. 2007. The function and regulation of the JARID1 family of histone H3 lysine 4 demethylases: The Myc connection. Cell Cycle 6: 1324-1328.
140. Secombe, J., Li, L., Carlos, L., and Eisenman, R.N. 2007. The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth. Genes & Dev. 21: 537-551.
141. Shi, Y. and Whetstine, J.R. 2007. Dynamic regulation of histone lysine methylation by demethylases. Mol. Cell 25: 1-14.
142. Shi, Y., Lan, F., Matson, C., Mulligan, P., Whetstine, J.R., Cole, P.A., and Casero, R.A. 2004. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119: 941-953.
143. Shi, Y.J., Matson, C., Lan, F., Iwase, S., Baba, T., and Shi, Y. 2005. Regulation of LSD1 histone demethylase activity by its associated factors. Mol. Cell 19: 857-864.
144. Siderius, L.E., Hamel, B.C., van Bokhoven, H., de Jager, F., van den Helm, B., Kremer, H., Heineman-de Boer, J.A., Ropers, H.H., and Mariman, E.C. 1999. X-linked mental retardation associated with cleft lip/palate maps to Xp11.3-q21.3. Am. J. Med. Genet. 85: 216-220.
145. Suzuki, T., Minehata, K., Akagi, K., Jenkins, N.A., and Copeland, N.G. 2006. Tumor suppressor gene identification using retroviral insertional mutagenesis in Blm-deficient mice. EMBO J. 25: 3422-3431.
146. Tahiliani, M., Mei, P., Fang, R., Leonor, T., Rutenberg, M., Shimizu, F., Li, J., Rao, A., and Shi, Y. 2007. The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature 447: 601-605.
147. Takeuchi, T. 1997. A gene trap approach to identify genes that control development. Dev. Growth Differ. 39: 127-134.
148. Takeuchi, T., Yamazaki, Y., Katoh-Fukui, Y., Tsuchiya, R., Kondo, S., Motoyama, J., and Higashinakagawa, T. 1995. Gene trap capture of a novel mouse gene, jumonji, required for neural tube formation. Genes & Dev. 9: 1211-1222.
149. Takeuchi, T., Kojima, M., Nakajima, K., and Kondo, S. 1999. jumonji gene is essential for the neurulation and cardiac development of mouse embryos with a C3H/He background. Mech. Dev. 86: 29-38.
150. Tan, K., Shaw, A.L., Madsen, B., Jensen, K., Taylor-Papadimitriou, J., and Freemont, P.S. 2003. Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. J. Biol. Chem. 278: 20507-20513.
151. Thompson, C.C., Sisk, J.M., and Beaudoin III, G.M. 2006. Hairless and Wnt signaling: Allies in epithelial stem cell differentiation. Cell Cycle 5: 1913-1917.
152. Toyoda, M., Shirato, H., Nakajima, K., Kojima, M., Takahashi, M., Kubota, M., Suzuki-Migishima, R., Motegi, Y., Yokoyama, M., and Takeuchi, T. 2003. jumonji downregulates cardiac cell proliferation by repressing cyclin D1 expression. Dev. Cell 5: 85-97.
153. Trewick, S.C., Henshaw, T.F., Hausinger, R.P., Lindahl, T., and Sedgwick, B. 2002. Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage. Nature 419: 174-178.
154. Trewick, S.C., McLaughlin, P.J., and Allshire, R.C. 2005. Methylation: Lost in hydroxylation? EMBO Rep. 6: 315-320.
155. Tsukada, Y., Fang, J., Erdjument-Bromage, H., Warren, M.E., Borchers, C.H., Tempst, P., and Zhang, Y. 2006. Histone demethylation by a family of JmjC domain-containing proteins. Nature 439: 811-816.
156. Tzschach, A., Lenzner, S., Moser, B., Reinhardt, R., Chelly, J., Fryns,
157. Valk-Lingbeek, M.E., Bruggeman, S.W., and van Lohuizen, M. 2004. Stem cells and cancer; The polycomb connection. Cell 118: 409-418.
158. van Zutven, L.J., Onen, E., Velthuizen, S.C., van Drunen, E., von Bergh, A.R., van den Heuvel-Eibrink, M.M., Veronese, A., Mecucci, C., Negrini, M., de Greef, G.E., et al. 2006. Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene. Genes Chromosomes Cancer 45: 437-446.
159. Vermeulen, M., Mulder, K.W., Denissov, S., Pijnappel, W.W., van Schaik, F.M., Varier, R.A., Baltissen, M.P., Stunnenberg, H.G., Mann, M., and Timmers, H.T. 2007. Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. Cell 131: 58-69.
160. Volcik, K.A., Zhu, H., Finnell, R.H., Shaw, G.M., Canfield, M., and Lammer, E.J. 2004. Evaluation of the jumonji gene and risk for spina bifida and congenital heart defects. Am. J. Med. Genet. A 126: 215-217.
161. Wang, H., Wang, L., Erdjument-Bromage, H., Vidal, M., Tempst, P., Jones, R.S., and Zhang, Y. 2004. Role of histone H2A ubiquitination in Polycomb silencing. Nature 431: 873-878.
162. Wang, Y., Wysocka, J., Sayegh, J., Lee, Y.H., Perlin, J.R., Leonelli, L., Sonbuchner, L.S., McDonald, C.H., Cook, R.G., Dou, Y., et al. 2004. Human PAD4 regulates histone arginine methylation levels via demethylimination. Science 306: 279-283.
163. Wang, J., Malloy, P.J., and Feldman, D. 2007a. Interactions of the vitamin D receptor with the corepressor hairless: Analysis of hairless mutants in atrichia with papular lesions. J. Biol. Chem. 282: 25231-25239.
164. Wang, J., Scully, K., Zhu, X., Cai, L., Zhang, J., Prefontaine, G.G., Krones, A., Ohgi, K.A., Zhu, P., Garcia-Bassets, I., et al. 2007b. Opposing LSD1 complexes function in developmental gene activation and repression programmes. Nature 446: 882-887.
165. Whetstine, J.R., Nottke, A., Lan, F., Huarte, M., Smolikov, S., Chen, Z., Spooner, E., Li, E., Zhang, G., Colaiacovo, M., et al. 2006. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125: 467-481.
166. Wissmann, M., Yin, N., Muller, J.M., Greschik, H., Fodor, B.D., Jenuwein, T., Vogler, C., Schneider, R., Gunther, T., Buettner, R., et al. 2007. Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression. Nat. Cell Biol. 9: 347-353.
167. Wolf, S.S., Patchev, V.K., and Obendorf, M. 2007. A novel variant of the putative demethylase gene, s-JMJD1C, is a coactivator of the AR. Arch. Biochem. Biophys. 460: 56-66.
168. Wu, J., Ellison, J., Salido, E., Yen, P., Mohandas, T., and Shapiro, L.J. 1994a. Isolation and characterization of XE169, a novel human gene that escapes X-inactivation. Hum. Mol. Genet. 3: 153-160.
169. Wu, J., Salido, E.C., Yen, P.H., Mohandas, T.K., Heng, H.H., Tsui, L.C., Park, J., Chapman, V.M., and Shapiro, L.J. 1994b. The murine Xe169 gene escapes X-inactivation like its human homologue. Nat. Genet. 7: 491-496.
170. Xi, Z.Q., Sun, J.J., Wang, X.F., Li, M.W., Liu, X.Z., Wang, L.Y., Zhu, X., Xiao, F., Li, J.M., Gong, Y., et al. 2007. HSPBAP1 is found extensively in the anterior temporal neocortex of patients with intractable epilepsy. Synapse 61: 741-747.
171. Xiang, Y., Zhu, Z., Han, G., Lin, H., Xu, L., and Chen, C.D. 2007a. JMJD3 is a histone H3K27 demethylase. Cell Res. 17: 850-857.
172. Xiang, Y., Zhu, Z., Han, G., Ye, X., Xu, B., Peng, Z., Ma, Y., Yu, Y., Lin, H., Chen, A.P., et al. 2007b. JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer. Proc. Natl. Acad. Sci. 104: 19226-19231.
173. Yamane, K., Toumazou, C., Tsukada, Y., Erdjument-Bromage, H., Tempst, P., Wong, J., and Zhang, Y. 2006. JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor. Cell 125: 483-495.
174. Yamane, K., Tateishi, K., Klose, R.J., Fang, J., Fabrizio, L.A., Erdjument-Bromage, H., Taylor-Papadimitriou, J., Tempst, P., and Zhang, Y. 2007. PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Mol. Cell 25: 801-812.
175. Yang, Z.Q., Imoto, I., Pimkhaokham, A., Shimada, Y., Sasaki, K., Oka, M., and Inazawa, J. 2001. A novel amplicon at 9p23-24 in squamous cell carcinoma of the esophagus that lies proximal to GASC1 and harbors NFIB. Jpn. J. Cancer Res. 92: 423-428.
176. Yang, M., Gocke, C.B., Luo, X., Borek, D., Tomchick, D.R., Machius, M., Otwinowski, Z., and Yu, H. 2006. Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase. Mol. Cell 23: 377-387.
177. You, A., Tong, J.K., Grozinger, C.M., and Schreiber, S.L. 2001. CoREST is an integral component of the CoREST-human histone deacetylase complex. Proc. Natl. Acad. Sci. 98: 1454-1458.