The polycomb repressive complex 1 protein BMI1 is required for constitutive heterochromatin formation and silencing in mammalian somatic cells

Journal of Biological Chemistry

Volumn 291, Issue 1, 2016, Pages 182-197

  Abdouh, Mohamed ^a   Hanna, Roy ^a   El Hajjar, Jida ^a   Flamier, Anthony ^a   Bernier, Gilbert ^a  

^a MAISONNEUVE ROSEMONT HOSPITAL   (Canada)

Author keywords

BMI1; BRCA1; Heterochromatin; Histone H2A; Polycomb

Indexed keywords

CELLS; CYTOLOGY; MAMMALS; PROTEINS; STEM CELLS;

BMI1; BRCA1; HETEROCHROMATIN; HISTONE H2A; POLYCOMB;

PLANTS (BOTANY);

BMI1 PROTEIN; BRCA1 PROTEIN; HETEROCHROMATIN PROTEIN 1; MEMBRANE PROTEIN; PROTEIN ATRX; PROTEIN DEK1; UNCLASSIFIED DRUG; BMI1 PROTEIN, HUMAN; BMI1 PROTEIN, MOUSE; HETEROCHROMATIN; HISTONE; ONCOPROTEIN; UBIQUITIN;

AMINO ACID SEQUENCE; ANIMAL CELL; ANIMAL TISSUE; ANTIBODY LABELING; ARTICLE; CELL NUCLEUS MEMBRANE; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; EMBRYO; HETEROCHROMATIN; HISTONE MODIFICATION; IMMUNOHISTOCHEMISTRY; MOUSE; NONHUMAN; OXYGENATION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEOMICS; SOMATIC CELL; TRANSMISSION ELECTRON MICROSCOPY; UBIQUITINATION; ANIMAL; BRAIN CORTEX; CYTOLOGY; DEFICIENCY; GENE SILENCING; GENETICS; HUMAN; MAMMAL; METABOLISM; NERVE CELL; NEURAL STEM CELL; NUCLEOTIDE REPEAT;

ANIMALS; BRCA1 PROTEIN; CEREBRAL CORTEX; GENE KNOCKDOWN TECHNIQUES; GENE SILENCING; HETEROCHROMATIN; HISTONES; HUMANS; MAMMALS; MICE; NEURAL STEM CELLS; NEURONS; NUCLEAR ENVELOPE; POLYCOMB REPRESSIVE COMPLEX 1; PROTO-ONCOGENE PROTEINS; REPETITIVE SEQUENCES, NUCLEIC ACID; UBIQUITIN;

EID: 84952901440     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M115.662403     Document Type: Article

References (78)

1. Fodor, B. D., Shukeir, N., Reuter, G., and Jenuwein, T. (2010) Mammalian Su(var) genes in chromatin control. Annu. Rev. Cell Dev. Biol. 26, 471-501
2. Kim, M., Trinh, B. N., Long, T. I., Oghamian, S., and Laird, P. W. (2004) Dnmt1 deficiency leads to enhanced microsatellite instability in mouse embryonic stem cells. Nucleic Acids Res. 32, 5742-5749
3. Kondo, Y., Shen, L., Ahmed, S., Boumber, Y., Sekido, Y., Haddad, B. R., and Issa, J. P. (2008) Downregulation of histone H3 lysine 9 methyltransferase G9a induces centrosome disruption and chromosome instability in cancer cells. PLoS ONE 3, e2037
4. Peng, J. C., and Karpen, G. H. (2008) Epigenetic regulation of heterochromatic DNA stability. Curr. Opin. Genet. Dev. 18, 204-211
5. Matsui, T., Leung, D., Miyashita, H., Maksakova, I. A., Miyachi, H., Kimura, H., Tachibana, M., Lorincz, M. C., and Shinkai, Y. (2010) Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature 464, 927-931
6. Rowe, H. M., Jakobsson, J., Mesnard, D., Rougemont, J., Reynard, S., Aktas, T., Maillard, P. V., Layard-Liesching, H., Verp, S., Marquis, J., Spitz, F., Constam, D. B., and Trono, D. (2010) KAP1 controls endogenous retroviruses in embryonic stem cells. Nature 463, 237-240
7. Pinheiro, I., Margueron, R., Shukeir, N., Eisold, M., Fritzsch, C., Richter, F. M., Mittler, G., Genoud, C., Goyama, S., Kurokawa, M., Son, J., Reinberg, D., Lachner, M., and Jenuwein, T. (2012) Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity. Cell 150, 948-960
8. Towbin, B. D., González-Aguilera, C., Sack, R., Gaidatzis, D., Kalck, V., Meister, P., Askjaer, P., and Gasser, S. M. (2012) Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery. Cell 150, 934-947
9. Black, J. C., and Whetstine, J. R. (2011) Chromatin landscape: methylation beyond transcription. Epigenetics 6, 9-15
10. Wang, R. H., Sengupta, K., Li, C., Kim, H. S., Cao, L., Xiao, C., Kim, S., Xu, X., Zheng, Y., Chilton, B., Jia, R., Zheng, Z. M., Appella, E., Wang, X. W., Ried, T., and Deng, C. X. (2008) ImpairedDNAdamage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell 14, 312-323
11. Kappes, F., Waldmann, T., Mathew, V., Yu, J., Zhang, L., Khodadoust, M. S., Chinnaiyan, A. M., Luger, K., Erhardt, S., Schneider, R., and Markovitz, D. M. (2011) The DEK oncoprotein is a Su(var) that is essential to heterochromatin integrity. Genes Dev. 25, 673-678
12. Maison, C., Bailly, D., Roche, D., Montes de Oca, R., Probst, A. V., Vassias, I., Dingli, F., Lombard, B., Loew, D., Quivy, J. P., and Almouzni, G. (2011) SUMOylation promotes de novo targeting of HP1α to pericentric heterochromatin. Nat. Genet. 43, 220-227
13. Fan, Y., Nikitina, T., Zhao, J., Fleury, T. J., Bhattacharyya, R., Bouhassira, E. E., Stein, A., Woodcock, C. L., and Skoultchi, A. I. (2005) Histone H1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation. Cell 123, 1199-1212
14. Iwase, S., Xiang, B., Ghosh, S., Ren, T., Lewis, P. W., Cochrane, J. C., Allis, C. D., Picketts, D. J., Patel, D. J., Li, H., and Shi, Y. (2011) ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome. Nat. Struct. Mol. Biol. 18, 769-776
15. Maison, C., and Almouzni, G. (2004) HP1 and the dynamics of heterochromatin maintenance. Nat. Rev. Mol. Cell Biol. 5, 296-304
16. Peters, A. H., O'Carroll, D., Scherthan, H., Mechtler, K., Sauer, S., Schöfer, C., Weipoltshammer, K., Pagani, M., Lachner, M., Kohlmaier, A., Opravil, S., Doyle, M., Sibilia, M., and Jenuwein, T. (2001) Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107, 323-337
17. Prasanth, S. G., Shen, Z., Prasanth, K. V., and Stillman, B. (2010) Human origin recognition complex is essential for HP1 binding to chromatin and heterochromatin organization. Proc. Natl. Acad. Sci. U.S.A. 107, 15093-15098
18. Huh, M. S., Price O'Dea, T., Ouazia, D., McKay, B. C., Parise, G., Parks, R. J., Rudnicki, M. A., and Picketts, D. J. (2012) Compromised genomic integrity impedes muscle growth after Atrx inactivation. J. Clin. Invest. 122, 4412-4423
19. Law, M. J., Lower, K. M., Voon, H. P., Hughes, J. R., Garrick, D., Viprakasit, V., Mitson, M., De Gobbi, M., Marra, M., Morris, A., Abbott, A., Wilder, S. P., Taylor, S., Santos, G. M., Cross, J., Ayyub, H., Jones, S., Ragoussis, J., Rhodes, D., Dunham, I., Higgs, D. R., and Gibbons, R. J. (2010) ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner. Cell 143, 367-378
20. Watson, L. A., Solomon, L. A., Li, J. R., Jiang, Y., Edwards, M., Shin-ya, K., Beier, F., and Bérubé, N. G. (2013) Atrx deficiency induces telomere dys-function, endocrine defects, and reduced life span. J. Clin. Invest. 123, 2049-2063
21. Kalb, R., Mallery, D. L., Larkin, C., Huang, J. T., and Hiom, K. (2014) BRCA1 Is a histone-H2A-specific ubiquitin ligase. Cell Rep. 8, 999-1005
22. Zhu, Q., Pao, G. M., Huynh, A. M., Suh, H., Tonnu, N., Nederlof, P. M., Gage, F. H., and Verma, I. M. (2011) BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nature 477, 179-184
23. Thakar, A., Parvin, J., and Zlatanova, J. (2010) BRCA1/BARD1 E3 ubiquitin ligase can modify histones H2A and H2B in the nucleosome particle. J. Biomol. Struct. Dyn. 27, 399-406
24. Sparmann, A., and van Lohuizen, M. (2006) Polycomb silencers control cell fate, development and cancer. Nat. Rev. Cancer 6, 846-856
25. Levine, S. S., Weiss, A., Erdjument-Bromage, H., Shao, Z., Tempst, P., and Kingston, R. E. (2002) The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans. Mol. Cell. Biol. 22, 6070-6078
26. Dellino, G. I., Schwartz, Y. B., Farkas, G., McCabe, D., Elgin, S. C., and Pirrotta, V. (2004) Polycomb silencing blocks transcription initiation. Mol. Cell 13, 887-893
27. Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P., and Reinberg, D. (2002) Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev. 16, 2893-2905
28. 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
29. Blackledge, N. P., Farcas, A. M., Kondo, T., King, H. W., McGouran, J. F., Hanssen, L. L., Ito, S., Cooper, S., Kondo, K., Koseki, Y., Ishikura, T., Long, H. K., Sheahan, T. W., Brockdorff, N., Kessler, B. M., Koseki, H., and Klose, R. J. (2014) Variant PRC1 complex-dependent H2A ubiquitylation drives PRC2 recruitment and polycomb domain formation. Cell 157, 1445-1459
30. Cooper, S., Dienstbier, M., Hassan, R., Schermelleh, L., Sharif, J., Blackledge, N. P., De Marco, V., Elderkin, S., Koseki, H., Klose, R., Heger, A., and Brockdorff, N. (2014) Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment. Cell Rep. 7, 1456-1470
31. Kleer, C. G., Cao, Q., Varambally, S., Shen, R., Ota, I., Tomlins, S. A., Ghosh, D., Sewalt, R. G., Otte, A. P., Hayes, D. F., Sabel, M. S., Livant, D., Weiss, S. J., Rubin, M. A., and Chinnaiyan, A. M. (2003) EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc. Natl. Acad. Sci. U.S.A. 100, 11606-11611
32. Lassman, A. B., Dai, C., Fuller, G. N., Vickers, A. J., and Holland, E. C. (2004) Overexpression of c-MYC promotes an undifferentiated phenotype in cultured astrocytes and allows elevated Ras and Akt signaling to induce gliomas from GFAP-expressing cells in mice. Neuron Glia Biol. 1, 157-163
33. Orian, J. M., Vasilopoulos, K., Yoshida, S., Kaye, A. H., Chow, C. W., and Gonzales, M. F. (1992) Overexpression of multiple oncogenes related to histological grade of astrocytic glioma. Br. J. Cancer 66, 106-112
34. Valk-Lingbeek, M. E., Bruggeman, S. W., and van Lohuizen, M. (2004) Stem cells and cancer; the polycomb connection. Cell 118, 409-418
35. Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar- Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G., Otte, A. P., Rubin, M. A., and Chinnaiyan, A. M. (2002) The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419, 624-629
36. Visser, H. P., Gunster, M. J., Kluin-Nelemans, H. C., Manders, E. M., Raaphorst, F. M., Meijer, C. J., Willemze, R., and Otte, A. P. (2001) The Polycomb group protein EZH2 is upregulated in proliferating, cultured human mantle cell lymphoma. Br. J. Haematol. 112, 950-958
37. Bruggeman, S. W., Valk-Lingbeek, M. E., van der Stoop, P. P., Jacobs, J. J., Kieboom, K., Tanger, E., Hulsman, D., Leung, C., Arsenijevic, Y., Marino, S., and van Lohuizen, M. (2005) Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice. Genes Dev. 19, 1438-1443
38. Chatoo, W., Abdouh, M., David, J., Champagne, M. P., Ferreira, J., Rodier, F., and Bernier, G. (2009) The polycomb group gene Bmi1 regulates antioxidant defenses in neurons by repressing p53 pro-oxidant activity. J. Neurosci. 29, 529-542
39. Jacobs, J. J., Kieboom, K., Marino, S., DePinho, R. A., and van Lohuizen, M. (1999) The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature 397, 164-168
40. Molofsky, A. V., Pardal, R., Iwashita, T., Park, I. K., Clarke, M. F., and Morrison, S. J. (2003) Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425, 962-967
41. Sharpless, N. E., and DePinho, R. A. (1999) The INK4A/ARF locus and its two gene products. Curr. Opin. Genet. Dev. 9, 22-30
42. Facchino, S., Abdouh, M., Chatoo, W., and Bernier, G. (2010) BMI1 confers radioresistance to normal and cancerous neural stem cells through recruitment of the DNA damage response machinery. J. Neurosci. 30, 10096-10111
43. Ismail, I. H., Andrin, C., McDonald, D., and Hendzel, M. J. (2010) BMI1- mediated histone ubiquitylation promotes DNA double-strand break repair. J. Cell Biol. 191, 45-60
44. Chagraoui, J., Hébert, J., Girard, S., and Sauvageau, G. (2011) An anticlastogenic function for the Polycomb Group gene Bmi1. Proc. Natl. Acad. Sci. U.S.A. 108, 5284-5289
45. Liu, J., Cao, L., Chen, J., Song, S., Lee, I. H., Quijano, C., Liu, H., Keyvanfar, K., Chen, H., Cao, L. Y., Ahn, B. H., Kumar, N. G., Rovira, I. I., Xu, X. L., van Lohuizen, M., Motoyama, N., Deng, C. X., and Finkel, T. (2009) Bmi1 regulates mitochondrial function and the DNA damage response pathway. Nature 459, 387-392
46. Hernández-Muñoz, I., Taghavi, P., Kuijl, C., Neefjes, J., and van Lohuizen, M. (2005) Association of BMI1 with polycomb bodies is dynamic and requires PRC2/EZH2 and the maintenance DNA methyltransferase DNMT1. Mol. Cell. Biol. 25, 11047-11058
47. Saurin, A. J., Shiels, C., Williamson, J., Satijn, D. P., Otte, A. P., Sheer, D., and Freemont, P. S. (1998) The human polycomb group complex associates with pericentromeric heterochromatin to form a novel nuclear domain. J. Cell Biol. 142, 887-898
48. Sewalt, R. G., Lachner, M., Vargas, M., Hamer, K. M., den Blaauwen, J. L., Hendrix, T., Melcher, M., Schweizer, D., Jenuwein, T., and Otte, A. P. (2002) Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins. Mol. Cell. Biol. 22, 5539-5553
49. Smigová, J., Juda, P., Cmarko, D., and Raška, I. (2011) Fine structure of the "PcG body" in human U-2 OS cells established by correlative light-electron microscopy. Nucleus 2, 219-228
50. Leeb, M., Pasini, D., Novatchkova, M., Jaritz, M., Helin, K., and Wutz, A. (2010) Polycomb complexes act redundantly to repress genomic repeats and genes. Genes Dev. 24, 265-276
51. Puschendorf, M., Terranova, R., Boutsma, E., Mao, X., Isono, K., Brykczynska, U., Kolb, C., Otte, A. P., Koseki, H., Orkin, S. H., van Lohuizen, M., and Peters, A. H. (2008) PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos. Nat. Genet. 40, 411-420
52. Saksouk, N., Barth, T. K., Ziegler-Birling, C., Olova, N., Nowak, A., Rey, E., Mateos-Langerak, J., Urbach, S., Reik, W., Torres-Padilla, M. E., Imhof, A., Déjardin, J., and Simboeck, E. (2014) Redundant mechanisms to form silent chromatin at pericentromeric regions rely on BEND3 and DNA methylation. Mol. Cell 56, 580-594
53. Gargiulo, G., Cesaroni, M., Serresi, M., de Vries, N., Hulsman, D., Bruggeman, S. W., Lancini, C., and van Lohuizen, M. (2013) In vivo RNAi screen for BMI1 targets identifies TGF-beta/BMP-ER stress pathways as key regulators of neural- and malignant glioma-stem cell homeostasis. Cancer Cell 23, 660-676
54. Tadeu, A. M., Ribeiro, S., Johnston, J., Goldberg, I., Gerloff, D., and Earnshaw, W. C. (2008) CENP-V is required for centromere organization, chromosome alignment and cytokinesis. EMBO J. 27, 2510-2522
55. Shumaker, D. K., Dechat, T., Kohlmaier, A., Adam, S. A., Bozovsky, M. R., Erdos, M. R., Eriksson, M., Goldman, A. E., Khuon, S., Collins, F. S., Jenuwein, T., and Goldman, R. D. (2006) Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc. Natl. Acad. Sci. U.S.A. 103, 8703-8708
56. Hwang, W. L., Deindl, S., Harada, B. T., and Zhuang, X. (2014) Histone H4 tail mediates allosteric regulation of nucleosome remodelling by linker DNA. Nature 512, 213-217
57. Hewish, D. R., and Burgoyne, L. A. (1973) Chromatin sub-structure. The digestion of chromatin DNA at regularly spaced sites by a nuclear deoxyribonuclease. Biochem. Biophys. Res. Commun. 52, 504-510
58. Kornberg, R. D., LaPointe, J. W., and Lorch, Y. (1989) Preparation of nucleosomes and chromatin. Methods Enzymol. 170, 3-14
59. Wu, C. (1980) The 5' ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature 286, 854-860
60. Abdouh, M., Facchino, S., Chatoo, W., Balasingam, V., Ferreira, J., and Bernier, G. (2009) BMI1 sustains human glioblastoma multiforme stem cell renewal. J. Neurosci. 29, 8884-8896
61. Schoeftner, S., Sengupta, A. K., Kubicek, S., Mechtler, K., Spahn, L., Koseki, H., Jenuwein, T., and Wutz, A. (2006) Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. EMBO J. 25, 3110-3122
62. Tavares, L., Dimitrova, E., Oxley, D., Webster, J., Poot, R., Demmers, J., Bezstarosti, K., Taylor, S., Ura, H., Koide, H., Wutz, A., Vidal, M., Elderkin, S., and Brockdorff, N. (2012) RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3. Cell 148, 664-678
63. Buchwald, G., van der Stoop, P., Weichenrieder, O., Perrakis, A., van Lohuizen, M., and Sixma, T. K. (2006) Structure and E3-ligase activity of the Ring-Ring complex of polycomb proteins Bmi1 and Ring1b. EMBO J. 25, 2465-2474
64. de Napoles, M., Mermoud, J. E., Wakao, R., Tang, Y. A., Endoh, M., Appanah, R., Nesterova, T. B., Silva, J., Otte, A. P., Vidal, M., Koseki, H., and Brockdorff, N. (2004) Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev. Cell 7, 663-676
65. Román-Trufero, M., Méndez-Gómez, H. R., Pérez, C., Hijikata, A., Fujimura, Y., Endo, T., Koseki, H., Vicario-Abejón, C., and Vidal, M. (2009) Maintenance of undifferentiated state and self-renewal of embryonic neural stem cells by Polycomb protein Ring1B. Stem Cells 27, 1559-1570
66. Francis, N. J., Kingston, R. E., and Woodcock, C. L. (2004) Chromatin compaction by a polycomb group protein complex. Science 306, 1574-1577
67. Meshorer, E., Yellajoshula, D., George, E., Scambler, P. J., Brown, D. T., and Misteli, T. (2006) Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev. Cell 10, 105-116
68. Varley, K. E., Gertz, J., Bowling, K. M., Parker, S. L., Reddy, T. E., Pauli- Behn, F., Cross, M. K., Williams, B. A., Stamatoyannopoulos, J. A., Crawford, G. E., Absher, D. M., Wold, B. J., and Myers, R. M. (2013) Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res. 23, 555-567
69. Kohli, R. M., and Zhang, Y. (2013) TET enzymes, TDG and the dynamics of DNA demethylation. Nature 502, 472-479
70. Scaffidi, P., and Misteli, T. (2006) Lamin A-dependent nuclear defects in human aging. Science 312, 1059-1063
71. Oberdoerffer, P., Michan, S., McVay, M., Mostoslavsky, R., Vann, J., Park, S. K., Hartlerode, A., Stegmuller, J., Hafner, A., Loerch, P., Wright, S. M., Mills, K. D., Bonni, A., Yankner, B. A., Scully, R., Prolla, T. A., Alt, F. W., and Sinclair, D. A. (2008) SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 135, 907-918
72. Larson, K., Yan, S. J., Tsurumi, A., Liu, J., Zhou, J., Gaur, K., Guo, D., Eickbush, T. H., and Li, W. X. (2012) Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis. PLoS Genet. 8, e1002473
73. Pegoraro, G., Kubben, N., Wickert, U., Göhler, H., Hoffmann, K., and Misteli, T. (2009) Ageing-related chromatin defects through loss of the NURD complex. Nat. Cell. Biol. 11, 1261-1267
74. Peng, J. C., and Karpen, G. H. (2009) Heterochromatic genome stability requires regulators of histone H3 K9 methylation. PLoS Genet. 5, e1000435
75. van der Lugt, N. M., Domen, J., Linders, K., van Roon, M., Robanus- Maandag, E., te Riele, H., van der Valk, M., Deschamps, J., Sofroniew, M., and van Lohuizen, M. (1994) Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene. Genes Dev. 8, 757-769
76. Kim, J., Kim, J. A., McGinty, R. K., Nguyen, U. T., Muir, T. W., Allis, C. D., and Roeder, R. G. (2013) The n-SET domain of Set1 regulates H2B ubiquitylation-dependent H3K4 methylation. Mol. Cell 49, 1121-1133
77. Wu, L., Lee, S. Y., Zhou, B., Nguyen, U. T., Muir, T. W., Tan, S., and Dou, Y. (2013) ASH2L regulates ubiquitylation signaling to MLL: trans-regulation of H3 K4 methylation in higher eukaryotes. Mol. Cell 49, 1108-1120
78. McGinty, R. K., Henrici, R. C., and Tan, S. (2014) Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome. Nature 514, 591-596