A role for widely interspaced zinc finger (WIZ) in retention of the G9a methyltransferase on chromatin

Journal of Biological Chemistry

Volumn 290, Issue 43, 2015, Pages 26088-26102

  Simon, Jeremy M ^a   Parker, Joel S ^a   Liu, Feng ^b   Rothbart, Scott B ^c   Ait Si ali, Slimane ^d   Strahl, Brian D ^a   Jin, Jian ^e   Davis, Ian J ^a   Mosley, Amber L ^f   Pattenden, Samantha G ^b  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b UNC Hamner Institute for Drug Safety Sciences   (United States)

^c VAN ANDEL RESEARCH INSTITUTE   (United States)

^d Université Sorbonne Paris Cité   (France)

^e MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^f INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKYLATION; AMINO ACIDS; ASSOCIATION REACTIONS; GENE EXPRESSION; METHYLATION; PROTEINS; ZINC;

DISCRETE FUNCTIONS; HETERODIMERIC COMPLEXES; HISTONE H3; LYSINE-9; METHYLTRANSFERASES; PROTEIN COMPLEXES; PROTEIN-PROTEIN INTERACTIONS; ZINC FINGER;

CHROMOSOMES;

2 CYCLOHEXYL N (1 ISOPROPYL 4 PIPERIDINYL) 6 METHOXY 7 [3 (1 PYRROLIDINYL)PROPOXY] 4 QUINAZOLINAMINE; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; G9A METHYLTRANSFERASE; HISTONE H3; HISTONE H3K9ME1; HISTONE H3K9ME2; METHYLTRANSFERASE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; WIDELY INTERSPACED ZINC FINGER PROTEIN; ZINC FINGER PROTEIN; CHROMATIN; KRUPPEL LIKE FACTOR; PROTEIN BINDING; WIZ PROTEIN, HUMAN;

ARTICLE; BINDING AFFINITY; CELLULAR DISTRIBUTION; CHROMATIN; COMBINATION CHEMOTHERAPY; CONTROLLED STUDY; DRUG ACTIVITY; ENZYME ACTIVITY; ENZYME INHIBITION; G9A GENE; GENE; GENE DISRUPTION; GENE EXPRESSION; GENE REPRESSION; GENE SILENCING; HISTONE METHYLATION; HUMAN; HUMAN CELL; MONOTHERAPY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEPLETION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN PURIFICATION; PROTEIN STABILITY; PROTEOMICS; SEQUENCE ANALYSIS; TRANSCRIPTION REGULATION; WIZ GENE; CHROMATIN IMMUNOPRECIPITATION; DNA METHYLATION; GENETICS; HEK293 CELL LINE; HELA CELL LINE; METABOLISM; PHYSIOLOGY;

CHROMATIN; CHROMATIN IMMUNOPRECIPITATION; DNA METHYLATION; GENE EXPRESSION; GENE KNOCKDOWN TECHNIQUES; HEK293 CELLS; HELA CELLS; HUMANS; KRUPPEL-LIKE TRANSCRIPTION FACTORS; METHYLTRANSFERASES; PROTEIN BINDING;

EID: 84944937871     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M115.654459     Document Type: Article

References (86)

1. Black, J. C., Van Rechem, C., and Whetstine, J. R. (2012) Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol. Cell 48, 491-507
2. Del Rizzo, P. A., and Trievel, R. C. (2014) Molecular basis for substrate recognition by lysine methyltransferases and demethylases. Biochim. Biophys. Acta 1839, 1404-1415
3. Herz, H. M., Garruss, A., and Shilatifard, A. (2013) SET for life: biochemical activities and biological functions of SET domain-containing proteins. Trends Biochem. Sci. 38, 621-639
4. Rea, S., Eisenhaber, F., O'Carroll, D., Strahl, B. D., Sun, Z. W., Schmid, M., Opravil, S., Mechtler, K., Ponting, C. P., Allis, C. D., and Jenuwein, T. (2000) Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406, 593-599
5. Mozzetta, C., Boyarchuk, E., Pontis, J., and Ait-Si-Ali, S. (2015) Sound of silence: the properties and functions of repressive Lys methyltransferases. Nature reviews. Mol. Cell Biol. 16, 499-513
6. Shankar, S. R., Bahirvani, A. G., Rao, V. K., Bharathy, N., Ow, J. R., and Taneja, R. (2013) G9a, a multipotent regulator of gene expression. Epigenetics 8, 16-22
7. Collins, R., and Cheng, X. (2010) A case study in cross-talk: the histone lysine methyltransferases G9a and GLP. Nucleic Acids Res. 38, 3503-3511
8. Shinkai, Y., and Tachibana, M. (2011) H3K9 methyltransferase G9a and the related molecule GLP. Genes Dev. 25, 781-788
9. Fritsch, L., Robin, P., Mathieu, J. R., Souidi, M., Hinaux, H., Rougeulle, C., Harel-Bellan, A., Ameyar-Zazoua, M., and Ait-Si-Ali, S. (2010) Asubset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex. Mol. Cell 37, 46-56
10. Mozzetta, C., Pontis, J., Fritsch, L., Robin, P., Portoso, M., Proux, C., Margueron, R., and Ait-Si-Ali, S. (2014) The histone H3 lysine 9 methyltransferases G9a and GLP regulate Polycomb repressive complex 2-mediated gene silencing. Mol. Cell 53, 277-289
11. Tachibana, M., Sugimoto, K., Fukushima, T., and Shinkai, Y. (2001) Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J. Biol. Chem. 276, 25309-25317
12. Weiss, T., Hergeth, S., Zeissler, U., Izzo, A., Tropberger, P., Zee, B. M., Dundr, M., Garcia, B. A., Daujat, S., and Schneider, R. (2010) Histone H1 variant-specific lysine methylation by G9a/KMT1C and Glp1/KMT1D. Epigenetics Chromatin 3, 7
13. Tachibana, M., Matsumura, Y., Fukuda, M., Kimura, H., and Shinkai, Y. (2008) G9a/GLP complexes independently mediate H3 K9 and DNA methylation to silence transcription. EMBO J. 27, 2681-2690
14. Trojer, P., Zhang, J., Yonezawa, M., Schmidt, A., Zheng, H., Jenuwein, T., and Reinberg, D. (2009) Dynamic histone H1 isotype 4 methylation and demethylation by histone lysine methyltransferase G9a/KMT1C and the Jumonji domain-containing JMJD2/KDM4 proteins. J. Biol. Chem. 284, 8395-8405
15. Wu, H., Chen, X., Xiong, J., Li, Y., Li, H., Ding, X., Liu, S., Chen, S., Gao, S., and Zhu, B. (2011) Histone methyltransferase G9a contributes to H3K27 methylation in vivo. Cell Res. 21, 365-367
16. Yu, Y., Song, C., Zhang, Q., DiMaggio, P. A., Garcia, B. A., York, A., Carey, M. F., and Grunstein, M. (2012) Histone H3 lysine 56 methylation regulates DNA replication through its interaction with PCNA. Mol. Cell 46, 7-17
17. Chin, H. G., Estève, P. O., Pradhan, M., Benner, J., Patnaik, D., Carey, M. F., and Pradhan, S. (2007) Automethylation of G9a and its implication in wider substrate specificity and HP1 binding. Nucleic Acids Res. 35, 7313-7323
18. Rathert, P., Dhayalan, A., Murakami, M., Zhang, X., Tamas, R., Jurkowska, R., Komatsu, Y., Shinkai, Y., Cheng, X., and Jeltsch, A. (2008) Protein lysine methyltransferase G9a acts on non-histone targets. Nat. Chem. Biol. 4, 344-346
19. Sampath, S. C., Marazzi, I., Yap, K. L., Sampath, S. C., Krutchinsky, A. N., Mecklenbräuker, I., Viale, A., Rudensky, E., Zhou, M. M., Chait, B. T., and Tarakhovsky, A. (2007) Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly. Mol. Cell 27, 596-608
20. Huang, J., Dorsey, J., Chuikov, S., Pérez-Burgos, L., Zhang, X., Jenuwein, T., Reinberg, D., and Berger, S. L. (2010) G9a and Glp methylate lysine 373 in the tumor suppressor p53. J. Biol. Chem. 285, 9636-9641
21. Biggar, K. K., and Li, S. S. (2015) Non-histone protein methylation as a regulator of cellular signalling and function. Nat. Rev. Mol. Cell Biol. 16, 5-17
22. Peters, A. H., Kubicek, S., Mechtler, K., O'Sullivan, R. J., Derijck, A. A., Perez-Burgos, L., Kohlmaier, A., Opravil, S., Tachibana, M., Shinkai, Y., Martens, J. H., and Jenuwein, T. (2003) Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol. Cell 12, 1577-1589
23. Jenuwein, T., Laible, G., Dorn, R., and Reuter, G. (1998) SET domain proteins modulate chromatin domains in eu- and heterochromatin. Cell. Mol. Life Sci. 54, 80-93
24. Tachibana, M., Sugimoto, K., Nozaki, M., Ueda, J., Ohta, T., Ohki, M., Fukuda, M., Takeda, N., Niida, H., Kato, H., and Shinkai, Y. (2002) G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev. 16, 1779-1791
25. Tachibana, M., Ueda, J., Fukuda, M., Takeda, N., Ohta, T., Iwanari, H., Sakihama, T., Kodama, T., Hamakubo, T., and Shinkai, Y. (2005) Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev. 19, 815-826
26. Matsumoto, K., Ishii, N., Yoshida, S., Shiosaka, S., Wanaka, A., and Tohyama, M. (1998) Molecular cloning and distinct developmental expression pattern of spliced forms of a novel zinc finger gene wiz in the mouse cerebellum. Brain Res. Mol. Brain Res. 61, 179-189
27. Miller, J., McLachlan, A. D., and Klug, A. (1985) Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 4, 1609-1614
28. Rosenberg, U. B., Schroder, C., Preiss, A., Kienlin, A., Cote, S., Riede, I., and Jackle, H. (1986) Structural homology of the product of the Drosophila Kruppel gene with Xenopus transcription factor Iiia. Nature 319, 336-339
29. Ueda, J., Tachibana, M., Ikura, T., and Shinkai, Y. (2006) Zinc finger protein Wiz links G9a/GLP histone methyltransferases to the co-repressor molecule CtBP. J. Biol. Chem. 281, 20120-20128
30. Vedadi, M., Barsyte-Lovejoy, D., Liu, F., Rival-Gervier, S., Allali-Hassani, A., Labrie, V., Wigle, T. J., Dimaggio, P. A., Wasney, G. A., Siarheyeva, A., Dong, A., Tempel, W., Wang, S. C., Chen, X., Chau, I., Mangano, T. J., Huang, X. P., Simpson, C. D., Pattenden, S. G., Norris, J. L., Kireev, D. B., Tripathy, A., Edwards, A., Roth, B. L., Janzen, W. P., Garcia, B. A., Petronis, A., Ellis, J., Brown, P. J., Frye, S. V., Arrowsmith, C. H., and Jin, J. (2011) A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat. Chem. Biol. 7, 566-574
31. Konze, K. D., Ma, A., Li, F., Barsyte-Lovejoy, D., Parton, T., Macnevin, C. J., Liu, F., Gao, C., Huang, X. P., Kuznetsova, E., Rougie, M., Jiang, A., Pattenden, S. G., Norris, J. L., James, L. I., Roth, B. L., Brown, P. J., Frye, S. V., Arrowsmith, C. H., Hahn, K. M., Wang, G. G., Vedadi, M., and Jin, J. (2013) An orally bioavailable chemical probe of the lysine methyltransferases EZH2 and EZH1. ACS Chem. Biol. 8, 1324-1334
32. Konze, K. D., Pattenden, S. G., Liu, F., Barsyte-Lovejoy, D., Li, F., Simon, J. M., Davis, I. J., Vedadi, M., and Jin, J. (2014) A chemical tool for in vitro and in vivo precipitation of lysine methyltransferase G9a. ChemMedChem 9, 549-553
33. Livak, K. J., and Schmittgen, T. D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-ΔΔC (T)) method. Methods 25, 402-408
34. Lassmann, T., Hayashizaki, Y., and Daub, C. O. (2009) TagDust: a program to eliminate artifacts from next generation sequencing data. Bioinformatics 25, 2839-2840
35. Langmead, B., Trapnell, C., Pop, M., and Salzberg, S. L. (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25
36. Shin, H., Liu, T., Manrai, A. K., and Liu, X. S. (2009) CEAS: cis-regulatory element annotation system. Bioinformatics 25, 2605-2606
37. ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57-74
38. Troyanskaya, O., Cantor, M., Sherlock, G., Brown, P., Hastie, T., Tibshirani, R., Botstein, D., and Altman, R. B. (2001) Missing value estimation methods for DNA microarrays. Bioinformatics 17, 520-525
39. Tusher, V. G., Tibshirani, R., and Chu, G. (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl. Acad. Sci. U. S. A. 98, 5116-5121
40. Mosley, A. L., Hunter, G. O., Sardiu, M. E., Smolle, M., Workman, J. L., Florens, L., and Washburn, M. P. (2013) Quantitative proteomics demonstrates that the RNA polymerase II subunits Rpb4 and Rpb7 dissociate during transcriptional elongation. Mol. Cell. Proteomics 12, 1530-1538
41. Smith-Kinnaman, W. R., Berna, M. J., Hunter, G. O., True, J. D., Hsu, P., Cabello, G. I., Fox, M. J., Varani, G., and Mosley, A. L. (2014) The interactome of the atypical phosphatase Rtr1 in Saccharomyces cerevisiae. Mol. Biosyst. 10, 1730-1741
42. Florens, L., and Washburn, M. P. (2006) Proteomic analysis by multidimensional protein identification technology. Methods Mol. Biol. 328, 159-175
43. Choi, H., Liu, G., Mellacheruvu, D., Tyers, M., Gingras, A. C., and Nesvizhskii, A. I. (2012) Analyzing protein-protein interactions from affinity purification-mass spectrometry data with SAINT. Curr. Protoc. Bioinformatics 39, 8.15.1-8.15.23
44. Choi, H., Larsen, B., Lin, Z. Y., Breitkreutz, A., Mellacheruvu, D., Fermin, D., Qin, Z. S., Tyers, M., Gingras, A. C., and Nesvizhskii, A. I. (2011) SAINT: probabilistic scoring of affinity purification-mass spectrometry data. Nat. Methods 8, 70-73
45. Mellacheruvu, D., Wright, Z., Couzens, A. L., Lambert, J. P., St-Denis, N. A., Li, T., Miteva, Y. V., Hauri, S., Sardiu, M. E., Low, T. Y., Halim, V. A., Bagshaw, R. D., Hubner, N. C., Al-Hakim, A., Bouchard, A., Faubert, D., Fermin, D., Dunham, W. H., Goudreault, M., Lin, Z. Y., Badillo, B. G., Pawson, T., Durocher, D., Coulombe, B., Aebersold, R., Superti-Furga, G., Colinge, J., Heck, A. J., Choi, H., Gstaiger, M., Mohammed, S., Cristea, I. M., Bennett, K. L., Washburn, M. P., Raught, B., Ewing, R. M., Gingras, A. C., and Nesvizhskii, A. I. (2013) The CRAPome: a contaminant repository for affinity purification-mass spectrometry data. Nat. Methods 10, 730-736
46. Frietze, S., O'Geen, H., Blahnik, K. R., Jin, V. X., and Farnham, P. J. (2010) ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes. PLoS ONE 5, e15082
47. Maier, V. K., Feeney, C. M., Taylor, J. E., Creech, A. L., Qiao, J. W., Szanto, A., Das, P. P., Chevrier, N., Cifuentes-Rojas, C., Orkin, S. H., Carr, S. A., Jaffe, J. D., Mertins, P., and Lee, J. T. (2015) Functional proteomic analysis of repressive histone methyltransferase complexes PRC2 and G9A reveals ZNF518B as a G9A regulator. Mol. Cell. Proteomics 14, 1435-1446
48. Baust, C., Baillie, G. J., and Mager, D. L. (2002) Insertional polymorphisms of ETn retrotransposons include a disruption of the wiz gene in C57BL/6 mice. Mamm. Genome 13, 423-428
49. Chaturvedi, C. P., Hosey, A. M., Palii, C., Perez-Iratxeta, C., Nakatani, Y., Ranish, J. A., Dilworth, F. J., and Brand, M. (2009) Dual role for the methyltransferase G9a in the maintenance of β-globin gene transcription in adult erythroid cells. Proc. Natl. Acad. Sci. U. S. A. 106, 18303-18308
50. Purcell, D. J., Jeong, K. W., Bittencourt, D., Gerke, D. S., and Stallcup, M. R. (2011) A distinct mechanism for coactivator versus corepressor function by histone methyltransferase G9a in transcriptional regulation. J. Biol. Chem. 286, 41963-41971
51. Bittencourt, D., Wu, D. Y., Jeong, K. W., Gerke, D. S., Herviou, L., Ianculescu, I., Chodankar, R., Siegmund, K. D., and Stallcup, M. R. (2012) G9a functions as a molecular scaffold for assembly of transcriptional coactivators on a subset of glucocorticoid receptor target genes. Proc. Natl. Acad. Sci. U. S. A. 109, 19673-19678
52. Lee, D. Y., Northrop, J. P., Kuo, M. H., and Stallcup, M. R. (2006) Histone H3 lysine 9 methyltransferase G9a is a transcriptional coactivator for nuclear receptors. J. Biol. Chem. 281, 8476-8485
53. Oh, S. T., Kim, K. B., Chae, Y. C., Kang, J. Y., Hahn, Y., and Seo, S. B. (2014) H3K9 histone methyltransferase G9a-mediated transcriptional activation of p21. FEBS Lett. 588, 685-691
54. Yuan, X., Feng, W., Imhof, A., Grummt, I., and Zhou, Y. (2007) Activation of RNA polymerase I transcription by cockayne syndrome group B protein and histone methyltransferase G9a. Mol. Cell 27, 585-595
55. Takatsuji, H., and Matsumoto, T. (1996) Target-sequence recognition by separate-type Cys2/His2 zinc finger proteins in plants. J. Biol. Chem. 271, 23368-23373
56. Takatsuji, H., Mori, M., Benfey, P. N., Ren, L., and Chua, N. H. (1992) Characterization of a zinc finger DNA-binding protein expressed specifically in petunia petals and seedlings. EMBO J. 11, 241-249
57. Takatsuji, H., Nakamura, N., and Katsumoto, Y. (1994) A new family of zinc finger proteins in petunia: structure, DNA sequence recognition, and floral organ-specific expression. Plant Cell 6, 947-958
58. Cléard, F., Delattre, M., and Spierer, P. (1997) SU (VAR) 3-7, a Drosophila heterochromatin-associated protein and companion of HP1 in the genomic silencing of position-effect variegation. EMBO J. 16, 5280-5288
59. Cléard, F., Matsarskaia, M., and Spierer, P. (1995) The modifier of positioneffect variegation Suvar (3) 7 of Drosophila: there are two alternative transcripts and seven scattered zinc fingers, each preceded by a tryptophan box. Nucleic Acids Res. 23, 796-802
60. Reuter, G., Giarre, M., Farah, J., Gausz, J., Spierer, A., and Spierer, P. (1990) Dependence of position-effect variegation in Drosophila on dose of a gene encoding an unusual zinc-finger protein. Nature 344, 219-223
61. Alexandre, E., Graba, Y., Fasano, L., Gallet, A., Perrin, L., De Zulueta, P., Pradel, J., Kerridge, S., and Jacq, B. (1996) The Drosophila Teashirt homeotic protein is a DNA-binding protein and modulo, a HOM-C regulated modifier of variegation, is a likely candidate for being a direct target gene. Mech. Dev. 59, 191-204
62. Waltzer, L., Vandel, L., and Bienz, M. (2001) Teashirt is required for transcriptional repression mediated by high Wingless levels. EMBO J. 20, 137-145
63. Caubit, X., Coré, N., Boned, A., Kerridge, S., Djabali, M., and Fasano, L. (2000) Vertebrate orthologues of the Drosophila region-specific patterning gene teashirt. Mech. Dev. 91, 445-448
64. Manfroid, I., Caubit, X., Kerridge, S., and Fasano, L. (2004) Three putative murine Teashirt orthologues specify trunk structures in Drosophila in the same way as the Drosophila teashirt gene. Development 131, 1065-1073
65. Bian, C., Chen, Q., and Yu, X. (2015) The zinc finger proteins ZNF644 and WIZ regulate the G9a/GLP complex for gene repression. eLife 4, eLife.05606;
66. Correction (2015) The zinc finger proteins ZNF644 and WIZ regulate the G9a/GLP complex for gene repression. eLife 4, eLife.08168
67. Snowden, A. W., Gregory, P. D., Case, C. C., and Pabo, C. O. (2002) Genespecific targeting of H3K9 methylation is sufficient for initiating repression in vivo. Curr. Biol. 12, 2159-2166
68. Stewart, M. D., Li, J., and Wong, J. (2005) Relationship between histone H3 lysine 9 methylation, transcription repression, and heterochromatin protein 1 recruitment. Mol. Cell. Biol. 25, 2525-2538
69. Dong, K. B., Maksakova, I. A., Mohn, F., Leung, D., Appanah, R., Lee, S., Yang, H. W., Lam, L. L., Mager, D. L., Schübeler, D., Tachibana, M., Shinkai, Y., and Lorincz, M. C. (2008) DNA methylation in ES cells requires the lysine methyltransferase G9a but not its catalytic activity. EMBO J. 27, 2691-2701
70. Epsztejn-Litman, S., Feldman, N., Abu-Remaileh, M., Shufaro, Y., Gerson, A., Ueda, J., Deplus, R., Fuks, F., Shinkai, Y., Cedar, H., and Bergman, Y. (2008) De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes. Nat. Struct. Mol. Biol. 15, 1176-1183
71. Bittencourt, D., Lee, B. H., Gao, L., Gerke, D. S., and Stallcup, M. R. (2014) Role of distinct surfaces of the G9a ankyrin repeat domain in histone and DNA methylation during embryonic stem cell self-renewal and differentiation. Epigenetics Chromatin 7, 27
72. Collins, R. E., Northrop, J. P., Horton, J. R., Lee, D. Y., Zhang, X., Stallcup, M. R., and Cheng, X. (2008) The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules. Nat. Struct. Mol. Biol. 15, 245-250
73. Wen, B., Wu, H., Shinkai, Y., Irizarry, R. A., and Feinberg, A. P. (2009) Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells. Nat. Genet. 41, 246-250
74. Caron, C., Pivot-Pajot, C., van Grunsven, L. A., Col, E., Lestrat, C., Rousseaux, S., and Khochbin, S. (2003) Cdyl: a new transcriptional co-repressor. EMBO Rep. 4, 877-882
75. Lahn, B. T., Tang, Z. L., Zhou, J., Barndt, R. J., Parvinen, M., Allis, C. D., and Page, D. C. (2002) Previously uncharacterized histone acetyltransferases implicated in mammalian spermatogenesis. Proc. Natl. Acad. Sci. U. S. A. 99, 8707-8712
76. Taunton, J., Hassig, C. A., and Schreiber, S. L. (1996) A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272, 408-411
77. Ding, Z., Gillespie, L. L., and Paterno, G. D. (2003) Human MI-ER1 α and β function as transcriptional repressors by recruitment of histone deacetylase 1 to their conserved ELM2 domain. Mol. Cell. Biol. 23, 250-258
78. Eissenberg, J. C., James, T. C., Foster-Hartnett, D. M., Hartnett, T., Ngan, V., and Elgin, S. C. (1990) Mutation in a heterochromatin-specific chromosomal protein is associated with suppression of position-effect variegation in Drosophila melanogaster. Proc. Natl. Acad. Sci. U. S. A. 87, 9923-9927
79. James, T. C., and Elgin, S. C. (1986) Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene. Mol. Cell. Biol. 6, 3862-3872
80. Saunders, W. S., Chue, C., Goebl, M., Craig, C., Clark, R. F., Powers, J. A., Eissenberg, J. C., Elgin, S. C., Rothfield, N. F., and Earnshaw, W. C. (1993) Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity. J. Cell Sci. 104, 573-582
81. Singh, P. B., Miller, J. R., Pearce, J., Kothary, R., Burton, R. D., Paro, R., James, T. C., and Gaunt, S. J. (1991) A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants. Nucleic Acids Res. 19, 789-794
82. Mulligan, P., Westbrook, T. F., Ottinger, M., Pavlova, N., Chang, B., Macia, E., Shi, Y. J., Barretina, J., Liu, J., Howley, P. M., Elledge, S. J., and Shi, Y. (2008) CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation. Mol. Cell 32, 718-726
83. Bantscheff, M., Hopf, C., Savitski, M. M., Dittmann, A., Grandi, P., Michon, A. M., Schlegl, J., Abraham, Y., Becher, I., Bergamini, G., Boesche, M., Delling, M., Dümpelfeld, B., Eberhard, D., Huthmacher, C., Mathieson, T., Poeckel, D., Reader, V., Strunk, K., Sweetman, G., Kruse, U., Neubauer, G., Ramsden, N. G., and Drewes, G. (2011) Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat. Biotechnol. 29, 255-265
84. Bunnage, M. E., Chekler, E. L., and Jones, L. H. (2013) Target validation using chemical probes. Nat. Chem. Biol. 9, 195-199
85. Weiss, W. A., Taylor, S. S., and Shokat, K. M. (2007) Recognizing and exploiting differences between RNAi and small-molecule inhibitors. Nat. Chem. Biol. 3, 739-744
86. Cole, P. A. (2008) Chemical probes for histone-modifying enzymes. Nat. Chem. Biol. 4, 590-597