Memories from the Polycomb group proteins

Annual Review of Genetics

Volumn 46, Issue , 2012, Pages 561-589

  Lanzuolo, Chiara ^a   Orlando, Valerio ^a  

^a IRCCS FONDAZIONE SANTA LUCIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; MEMBRANE PROTEIN; PHO REPRESSIVE COMPLEX; POLYCOMB GROUP PROTEIN; PRC1 COMPLEX; PRC2 COMPLEX; UNCLASSIFIED DRUG; UNTRANSLATED RNA;

BIOLOGY; CELL DIVISION; CHROMATIN; ENZYME ACTIVITY; EPIGENETICS; GENE STRUCTURE; GENETIC TRANSCRIPTION; HELPER CELL; HUMAN; MODULATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW;

ANIMALS; CHROMATIN ASSEMBLY AND DISASSEMBLY; CHROMOSOMES, INSECT; DROSOPHILA; DROSOPHILA PROTEINS; ENZYME ACTIVATION; EPIGENESIS, GENETIC; HISTONE-LYSINE N-METHYLTRANSFERASE; HISTONES; HUMANS; POLYCOMB-GROUP PROTEINS; PROTEIN INTERACTION MAPPING; REPRESSOR PROTEINS; RNA, UNTRANSLATED; TRANSCRIPTION, GENETIC; UBIQUITINATION;

DROSOPHILA MELANOGASTER;

EID: 84870169122     PISSN: 00664197     EISSN: 15452948     Source Type: Book Series    
DOI: 10.1146/annurev-genet-110711-155603     Document Type: Review

References (220)

1. Agger K, Cloos PA, Christensen J, Pasini D, Rose S, et al. 2007. UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature 449:731-34
2. Akam M. 1987. Themolecular basis for metameric pattern in the Drosophila embryo. Development 101:1- 22
3. Akasaka T, van LohuizenM, van der Lugt N, Mizutani-Koseki Y, Kanno M, et al. 2001. Mice doubly deficient for the Polycomb Group genesMel18 and Bmi1 reveal synergy and requirement for maintenance but not initiation of Hox gene expression. Development 128:1587-97
4. Alabert C, Groth A. 2012. Chromatin replication and epigenome maintenance. Nat. Rev. Mol. Cell Biol. 13:153-67
5. Aoto T, Saitoh N, Sakamoto Y, Watanabe S, Nakao M. 2008. Polycomb group protein-associated chromatin is reproduced in post-mitotic G1 phase and is required for S phase progression. J. Biol. Chem. 283:18905-15
6. Bae E, Calhoun VC, Levine M, Lewis EB, Drewell RA. 2002. Characterization of the intergenic RNA profile at abdominal-A and abdominal-B in the Drosophila bithorax complex. Proc. Natl. Acad. Sci. USA 99:16847-52
7. Bantignies F, Grimaud C, Lavrov S, Gabut M, Cavalli G. 2003. Inheritance of Polycomb-dependent chromosomal interactions in Drosophila. Genes Dev. 17:2406-20
8. Bantignies F, Roure V, Comet I, Leblanc B, Schuettengruber B, et al. 2011. Polycomb-dependent regulatory contacts between distant Hox loci in Drosophila. Cell 144:214-26
9. Barna M, Merghoub T, Costoya JA, Ruggero D, Branford M, et al. 2002. Plzf mediates transcriptional repression of HoxD gene expression through chromatin remodeling. Dev. Cell 3:499-510
10. Ben-Saadon R, Zaaroor D, Ziv T, Ciechanover A. 2006. The Polycomb protein Ring1B generates self atypical mixed ubiquitin chains required for its in vitro histone H2A ligase activity. Mol. Cell 24:701-11
11. Benson LJ, Gu Y, Yakovleva T, Tong K, Barrows C, et al. 2006. Modifications of H3 and H4 during chromatin replication, nucleosome assembly, and histone exchange. J. Biol. Chem. 281:9287-96
12. Bentley ML, Corn JE, Dong KC, Phung Q, Cheung TK, Cochran AG. 2011. Recognition of UbcH5c and the nucleosome by the Bmi1/Ring1b ubiquitin ligase complex. EMBO J. 30:3285-97
13. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, et al. 2006. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:315-26
14. Bernstein E, Duncan EM, Masui O, Gil J, Heard E, Allis CD. 2006. Mouse Polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin. Mol. Cell. Biol. 26:2560-69
15. Boulay G, Rosnoblet C, Guerardel C, Angrand PO, Leprince D. 2011. Functional characterization of human Polycomb-like 3 isoforms identifies them as components of distinct EZH2 protein complexes. Biochem. J. 434:333-42
16. Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, et al. 2006. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441:349-53
17. Bracken AP, Dietrich N, Pasini D, Hansen KH, Helin K. 2006. Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev. 20:1123-36
18. Breiling A, O'Neill LP, D'Eliseo D, Turner BM, Orlando V. 2004. Epigenome changes in active and inactive Polycomb-group-controlled regions. EMBO Rep. 5:976-82
19. Breiling A, Turner BM, Bianchi ME, Orlando V. 2001. General transcription factors bind promoters repressed by Polycomb group proteins. Nature 412:651-55
20. Brockdorff N. 2011. Chromosome silencing mechanisms in X-chromosome inactivation: unknown unknowns. Development 138:5057-65
21. Brookes E, de Santiago I, Hebenstreit D, MorrisKJ, Carroll T, et al. 2012. Polycomb associates genomewide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs. Cell Stem Cell 10:157-70
22. Buchenau P, Hodgson J, Strutt H, Arndt-Jovin DJ. 1998. The distribution of Polycomb-group proteins during cell division and development in Drosophila embryos: impact on models for silencing. J. Cell Biol. 141:469-81
23. Cabianca DS, Casa V, Bodega B, Xynos A, Ginelli E, et al. 2012. A long ncRNA links copy number variation to a polycomb/trithorax epigenetic switch in FSHD muscular dystrophy. Cell 149:819-31
24. Cao R, Tsukada Y, Zhang Y. 2005. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol. Cell 20:845-54
25. Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, et al. 2002. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298:1039-43
26. CaoR, Zhang Y. 2004. SUZ12 is required for both the histonemethyltransferase activity and the silencing function of the EED-EZH2 complex. Mol. Cell 15:57-67
27. Caretti G, Di Padova M, Micales B, Lyons GE, Sartorelli V. 2004. The PolycombEzh2methyltransferase regulates muscle gene expression and skeletal muscle differentiation. Genes Dev. 18:2627-38
28. Casanova M, Preissner T, Cerase A, Poot R, Yamada D, et al. 2011. Polycomblike 2 facilitates the recruitment of PRC2 Polycomb group complexes to the inactive X chromosome and to target loci in embryonic stem cells. Development 138:1471-82
29. Chambeyron S, Bickmore WA. 2004. Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes Dev. 18:1119-30
30. Chambeyron S, Da Silva NR, Lawson KA, Bickmore WA. 2005. Nuclear re-organisation of the HoxB complex during mouse embryonic development. Development 132:2215-23
31. Chen S, Bohrer LR, Rai AN, Pan Y, Gan L, et al. 2010. Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. Nat. Cell Biol. 12:1108-14
32. Cheutin T, Cavalli G. 2012. Progressive Polycomb assembly on H3K27me3 compartments generates Polycomb bodies with developmentally regulated motion. PLoS Genet. 8:e1002465
33. Chu C, Qu K, Zhong FL, Artandi SE, Chang HY. 2011. Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol. Cell 44:667-78
34. Cleard F, Moshkin Y, Karch F, Maeda RK. 2006. Probing long-distance regulatory interactions in the Drosophila melanogaster bithorax complex using Dam identification. Nat. Genet. 38:931-5
35. Cmarko D, Verschure PJ, Otte AP, van Driel R, Fakan S. 2003. Polycomb group gene silencing proteins are concentrated in the perichromatin compartment of the mammalian nucleus. J. Cell Sci. 116:335-43
36. Core N, Bel S, Gaunt SJ, Aurrand-Lions M, Pearce J, et al. 1997. Altered cellular proliferation and mesoderm patterning in Polycomb-M33-deficient mice. Development 124:721-29
37. Cremer T, Cremer M, Dietzel S, Muller S, Solovei I, Fakan S. 2006. Chromosome territories: a functional nuclear landscape. Curr. Opin. Cell Biol. 18:307-16
38. de Napoles M, Mermoud JE, Wakao R, Tang YA, Endoh M, et al. 2004. Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev. Cell 7:663-76
39. De Santa F, Totaro MG, Prosperini E, Notarbartolo S, Testa G, Natoli G. 2007. The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of Polycomb-mediated gene silencing. Cell 130:1083-94
40. Deal RB, Henikoff JG, Henikoff S. 2010. Genome-wide kinetics of nucleosome turnover determined by metabolic labeling of histones. Science 328:1161-64
41. Dejardin J, Rappailles A, Cuvier O, Grimaud C, Decoville M, et al. 2005. Recruitment of Drosophila Polycomb group proteins to chromatin by DSP1. Nature 434:533-38
42. del Mar Lorente M, Marcos-Gutierrez C, Perez C, Schoorlemmer J, Ramirez A, et al. 2000. Loss- and gain-of-function mutations show a Polycomb group function for Ring1A in mice. Development 127:5093- 100
43. Dellino GI, Schwartz YB, Farkas G, McCabe D, Elgin SC, Pirrotta V. 2004. Polycomb silencing blocks transcription initiation. Mol. Cell 13:887-93
44. Dietrich N, Lerdrup M, Landt E, Agrawal-Singh S, Bak M, et al. 2012. REST-mediated recruitment of Polycomb repressor complexes in mammalian cells. PLoS Genet. 8:e1002494
45. Donohoe ME, Zhang X, McGinnis L, Biggers J, Li E, Shi Y. 1999. Targeted disruption of mouse Yin Yang 1 transcription factor results in peri-implantation lethality. Mol. Cell. Biol. 19:7237-44
46. Enderle D, Beisel C, Stadler MB, Gerstung M, Athri P, Paro R. 2011. Polycomb preferentially targets stalled promoters of coding and noncoding transcripts. Genome Res. 21:216-26
47. Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, et al. 2011. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473:43-49
48. Eskeland R, Leeb M, Grimes GR, Kress C, Boyle S, et al. 2010. Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination. Mol. Cell 38:452-64
49. Ficz G, Heintzmann R, Arndt-Jovin DJ. 2005. Polycomb group protein complexes exchange rapidly in living Drosophila. Development 132:3963-76
50. Filion GJ, van Bemmel JG, Braunschweig U, Talhout W, Kind J, et al. 2010. Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell 143:212-24
51. Fischle W, Wang Y, Jacobs SA, Kim Y, Allis CD, Khorasanizadeh S. 2003. Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev. 17:1870-81
52. Fisher CL, Fisher AG. 2011. Chromatin states in pluripotent, differentiated, and reprogrammed cells. Curr. Opin. Genet. Dev. 21:140-46
53. Francis NJ, Follmer NE, Simon MD, Aghia G, Butler JD. 2009. Polycomb proteins remain bound to chromatin and DNA during DNA replication in vitro. Cell 137:110-22
54. Francis NJ, Kingston RE, Woodcock CL. 2004. Chromatin compaction by a Polycomb group protein complex. Science 306:1574-77
55. Franke A, DeCamillis M, Zink D, Cheng N, Brock HW, Paro R. 1992. Polycomb and polyhomeotic are constituents of a multimeric protein complex in chromatin of Drosophila melanogaster. EMBO J. 11:2941-50
56. Gabellini D, Green MR, Tupler R. 2002. Inappropriate gene activation in FSHD: a repressor complex binds a chromosomal repeat deleted in dystrophic muscle. Cell 110:339-48
57. Gao Z, Zhang J, Bonasio R, Strino F, Sawai A, et al. 2012. PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. Mol. Cell 45:344-56
58. Garcia E, Marcos-Gutierrez C, del Mar Lorente M, Moreno JC, Vidal M. 1999. RYBP, a new repressor protein that interacts with components of themammalian Polycomb complex, and with the transcription factor YY1. EMBO J. 18:3404-18
59. Gearhart MD, Corcoran CM, Wamstad JA, Bardwell VJ. 2006. Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets. Mol. Cell. Biol. 26:6880-89
60. Gehani SS, Agrawal-Singh S, Dietrich N, Christophersen NS, Helin K, Hansen K. 2010. Polycomb group protein displacement and gene activation through MSK-dependent H3K27me3S28 phosphorylation. Mol. Cell 39:886-900
61. Grau DJ, Chapman BA, Garlick JD, Borowsky M, Francis NJ, Kingston RE. 2011. Compaction of chromatin by diverse Polycomb group proteins requires localized regions of high charge. Genes Dev. 25:2210-21
62. Groth A, Rocha W, Verreault A, Almouzni G. 2007. Chromatin challenges during DNA replication and repair. Cell 128:721-33
63. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, et al. 2010. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071-76
64. Hansen KH, Bracken AP, Pasini D, Dietrich N, Gehani SS, et al. 2008. A model for transmission of the H3K27me3 epigenetic mark. Nat. Cell Biol. 10:1291-300
65. Hawkins RD, Hon GC, Lee LK, Ngo Q, Lister R, et al. 2010. Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell 6:479-91
66. He A, Shen X, Ma Q, Cao J, von Gise A, et al. 2012. PRC2 directly methylates GATA4 and represses its transcriptional activity. Genes Dev. 26:37-42
67. He Y, Dupree J, Wang J, Sandoval J, Li J, et al. 2007. The transcription factor Yin Yang 1 is essential for oligodendrocyte progenitor differentiation. Neuron 55:217-30
68. Hennig L, Derkacheva M. 2009. Diversity of Polycomb group complexes in plants: same rules, different players? Trends Genet. 25:414-23
69. Herranz N, Pasini D, Diaz VM, Franci C, Gutierrez A, et al. 2008. Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor. Mol. Cell. Biol. 28:4772-81
70. Hong S, Cho YW, Yu LR, Yu H, Veenstra TD, Ge K. 2007. Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases. Proc. Natl. Acad. Sci. USA 104:18439-44
71. Hunkapiller J, Shen Y, Diaz A, Cagney G, McCleary D, et al. 2012. Polycomb-like 3 promotes Polycomb repressive complex 2 binding to CpG islands and embryonic stem cell self-renewal. PLoS Genet. 8:e1002576
72. Ismail IH, Gagne JP, Caron MC, McDonald D, Xu Z, et al. 2012. CBX4-mediated SUMO modification regulates BMI1 recruitment at sites of DNA damage. Nucleic Acids Res. 40:5497-5510
73. Jackson V. 1990. In vivo studies on the dynamics of histone-DNA interaction: evidence for nucleosome dissolution during replication and transcription and a low level of dissolution independent of both. Biochemistry 29:719-31
74. Jeon Y, Lee JT. 2011. YY1 tethers Xist RNA to the inactive X nucleation center. Cell 146:119-33
75. Juan AH, Kumar RM, Marx JG, Young RA, Sartorelli V. 2009. Mir-214-dependent regulation of the Polycomb protein Ezh2 in skeletal muscle and embryonic stem cells. Mol. Cell 36:61-74
76. KageyMH, Melhuish TA, WottonD. 2003. The Polycomb protein Pc2 is aSUMO E3. Cell 113:127-37
77. Kalenik JL, Chen D, BradleyME, Chen SJ, Lee TC. 1997. Yeast two-hybrid cloning of a novel zinc finger protein that interacts with the multifunctional transcription factor YY1. Nucleic Acids Res. 25:843-49
78. Kanduri C, Thakur N, Pandey RR. 2006. The length of the transcript encoded from the Kcnq1ot1 antisense promoter determines the degree of silencing. EMBO J. 25:2096-106
79. Kaneko S, Li G, Son J, Xu CF, Margueron R, et al. 2010. Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Genes Dev. 24:2615-20
80. Kang X, Qi Y, Zuo Y, Wang Q, Zou Y, et al. 2010. SUMO-specific protease 2 is essential for suppression of Polycomb group protein-mediated gene silencing during embryonic development. Mol. Cell 38:191- 201
81. Kanhere A, Viiri K, Araujo CC, Rasaiyaah J, Bouwman RD, et al. 2010. Short RNAs are transcribed from repressed Polycomb target genes and interact with Polycomb repressive complex-2. Mol. Cell 38:675-88
82. Kharchenko PV, Alekseyenko AA, Schwartz YB, Minoda A, Riddle NC, et al. 2011. Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471:480-85
83. Kheradmand Kia S, Solaimani Kartalaei P, Farahbakhshian E, Pourfarzad F, von Lindern M, Verrijzer C. 2009. EZH2-dependent chromatin looping controls INK4a and INK4b, but not ARF, during human progenitor cell differentiation and cellular senescence. Epigenet. Chromatin 2:16
84. Kim H, Kang K, Kim J. 2009. AEBP2 as a potential targeting protein for Polycomb repression complex PRC2. Nucleic Acids Res. 37:2940-50
85. King IF, Emmons RB, Francis NJ, Wild B, Muller J, et al. 2005. Analysis of a Polycomb group protein defines regions that link repressive activity on nucleosomal templates to in vivo function. Mol. Cell. Biol. 25:6578-91
86. Klymenko T, Papp B, Fischle W, KocherT, SchelderM, et al. 2006. A Polycomb group protein complex with sequence-specificDNA-binding and selective methyl-lysine-binding activities. GenesDev. 20:1110- 22
87. Kohlmaier A, Savarese F, Lachner M, Martens J, Jenuwein T, Wutz A. 2004. A chromosomal memory triggered by Xist regulates histone methylation in X inactivation. PLoS Biol. 2:e171
88. Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, et al. 2011. Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene 30:1956-62
89. Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, et al. 2008. Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet. 4:e1000242
90. Kuzmichev A, Margueron R, Vaquero A, Preissner TS, Scher M, et al. 2005. Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation. Proc. Natl. Acad. Sci. USA 102:1859-64
91. Lagarou A, Mohd-Sarip A, Moshkin YM, Chalkley GE, Bezstarosti K, et al. 2008. dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing. Genes Dev. 22:2799-810
92. Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, et al. 2007. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature 449:689-94
93. Landeira D, Sauer S, Poot R, Dvorkina M, Mazzarella L, et al. 2010. Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators. Nat. Cell Biol. 12:618-24
94. Lanzuolo C, Lo Sardo F, Diamantini A, Orlando V. 2011. PcG complexes set the stage for epigenetic inheritance of gene silencing in early S phase before replication. PLoS Genet. 7:e1002370
95. Lanzuolo C, Lo Sardo F, Orlando V. 2012. Concerted epigenetic signatures inheritance at PcG targets through replication. Cell Cycle 11:1296-300
96. Lanzuolo C, Orlando V. 2007. The function of the epigenome in cell reprogramming. Cell Mol. Life Sci. 64:1043-62
97. Lanzuolo C, Roure V, Dekker J, Bantignies F, Orlando V. 2007. Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex. Nat. Cell Biol. 9:1167-74
98. Lau PN, Cheung P. 2011. Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes Polycomb silencing. Proc. Natl. Acad. Sci. USA 108:2801-6
99. Lee MG, Norman J, Shilatifard A, Shiekhattar R. 2007. Physical and functional association of a trimethyl H3K4 demethylase and Ring6a/MBLR, a Polycomb-like protein. Cell 128:877-87
100. Lee MG, Villa R, Trojer P, Norman J, YanKP, et al. 2007. Demethylation ofH3K27 regulates Polycomb recruitment and H2A ubiquitination. Science 318:447-50
101. Levine SS, Weiss A, Erdjument-Bromage H, Shao Z, Tempst P, Kingston RE. 2002. The core of the Polycomb repressive complex is compositionally and functionally conserved in flies and humans. Mol. Cell. Biol. 22:6070-78
102. Lewis EB. 1978. A gene complex controlling segmentation in Drosophila. Nature 276:565-70
103. Li G, Margueron R, Ku M, Chambon P, Bernstein BE, Reinberg D. 2010. Jarid2 and PRC2, partners in regulating gene expression. Genes Dev. 24:368-80
104. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, et al. 2009. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289-93
105. Luis NM, Morey L, Mejetta S, Pascual G, Janich P, et al. 2011. Regulation of human epidermal stem cell proliferation and senescence requires polycomb-dependent and -independent functions of Cbx4. Cell Stem Cell 9:233-46
106. Lynch MD, Smith AJ, De Gobbi M, Flenley M, Hughes JR, et al. 2011. An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment. EMBO J. 31:317-29
107. Maenner S, Blaud M, Fouillen L, Savoye A, Marchand V, et al. 2010. 2-D structure of the A region of Xist RNA and its implication for PRC2 association. PLoS Biol. 8:e1000276
108. Mao YS, Zhang B, Spector DL. 2011. Biogenesis and function of nuclear bodies. Trends Genet. 27:295- 306
109. Margueron R, Justin N, Ohno K, Sharpe ML, Son J, et al. 2009. Role of the Polycomb protein EED in the propagation of repressive histone marks. Nature 461:762-67
110. Margueron R, Li G, Sarma K, Blais A, Zavadil J, et al. 2008. Ezh1 andEzh2maintain repressive chromatin through different mechanisms. Mol. Cell 32:503-18
111. Margueron R, Reinberg D. 2011. The Polycomb complex PRC2 and its mark in life. Nature 469:343-49
112. Martin-Perez D, Piris MA, Sanchez-Beato M. 2010. Polycomb proteins in hematologic malignancies. Blood 116:5465-75
113. Mejetta S, Morey L, Pascual G, Kuebler B, Mysliwiec MR, et al. 2011. Jarid2 regulates mouse epidermal stem cell activation and differentiation. EMBO J. 30:3635-46
114. Mendenhall EM, Koche RP, Truong T, Zhou VW, Issac B, et al. 2010. GC-rich sequence elements recruit PRC2 in mammalian ES cells. PLoS Genet. 6:e1001244
115. Mercer TR, Gerhardt DJ, Dinger ME, Crawford J, Trapnell C, et al. 2012. Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat. Biotechnol. 30:99-104
116. Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, et al. 2007. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448:553-60
117. Min IM, Waterfall JJ, Core LJ, Munroe RJ, Schimenti J, Lis JT. 2011. Regulating RNA polymerase pausing and transcription elongation in embryonic stem cells. Genes Dev. 25:742-54
118. Min J, Zhang Y, Xu RM. 2003. Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27. Genes Dev. 17:1823-28
119. Mishra RK, Mihaly J, Barges S, Spierer A, Karch F, et al. 2001. The iab-7 Polycomb response element maps to a nucleosome-free region of chromatin and requires bothGAGAand pleiohomeotic for silencing activity. Mol. Cell. Biol. 21:1311-18
120. Mohd-Sarip A, Cleard F, Mishra RK, Karch F, Verrijzer CP. 2005. Synergistic recognition of an epigenetic DNA element by Pleiohomeotic and a Polycomb core complex. Genes Dev. 19:1755-60
121. Mohd-Sarip A, van der Knaap JA, Wyman C, Kanaar R, Schedl P, Verrijzer CP. 2006. Architecture of a Polycomb nucleoprotein complex. Mol. Cell 24:91-100
122. Mohd-Sarip A, Venturini F, Chalkley GE, Verrijzer CP. 2002. Pleiohomeotic can link polycomb to DNA and mediate transcriptional repression. Mol. Cell. Biol. 22:7473-83
123. Morey L, Pascual G, Cozzuto L, Roma G, Wutz A, et al. 2012. Nonoverlapping functions of the Polycomb group Cbx family of proteins in embryonic stem cells. Cell Stem Cell 10:47-62
124. Morin-Kensicki EM, Faust C, LaMantia C, Magnuson T. 2001. Cell and tissue requirements for the gene eed during mouse gastrulation and organogenesis. Genesis 31:142-46
125. Mousavi K, Zare H, Wang AH, Sartorelli V. 2011. Polycomb protein Ezh1 promotes RNA polymerase II elongation. Mol. Cell 45:255-62
126. Muller J, Kassis JA. 2006. Polycomb response elements and targeting of Polycomb group proteins in Drosophila. Curr. Opin. Genet. Dev. 16:476-84
127. Nekrasov M, Klymenko T, Fraterman S, Papp B, Oktaba K, et al. 2007. Pcl-PRC2 is needed to generate high levels of H3-K27 trimethylation at Polycomb target genes. EMBO J. 26:4078-88
128. Nekrasov M, Wild B, Muller J. 2005. Nucleosome binding and histone methyltransferase activity of Drosophila PRC2. EMBO Rep. 6:348-53
129. Nguyen LK, Munoz-Garcia J, Maccario H, Ciechanover A, Kolch W, Kholodenko BN. 2011. Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system. PLoS Comput. Biol. 7:e1002317
130. Noordermeer D, Leleu M, Splinter E, Rougemont J, De Laat W, Duboule D. 2011. The dynamic architecture of Hox gene clusters. Science 334:222-25
131. O'Carroll D, Erhardt S, Pagani M, Barton SC, Surani MA, Jenuwein T. 2001. The Polycomb-group gene Ezh2 is required for early mouse development. Mol. Cell. Biol. 21:4330-36
132. Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y. 2002. A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. Science 296:1132-36
133. Ohno K, McCabe D, Czermin B, Imhof A, Pirrotta V. 2008. ESC, ESCL and their roles in Polycomb group mechanisms. Mech. Dev. 125:527-41
134. Oktaba K, Gutierrez L, Gagneur J, Girardot C, Sengupta AK, et al. 2008. Dynamic regulation by Polycomb group protein complexes controls pattern formation and the cell cycle in Drosophila. Dev. Cell 15:877-89
135. Orlando V, Jane EP, Chinwall V, Harte, PJ, Paro R. 1998. Binding of trithorax and Polycomb proteins to the bithorax complex: dynamic changes during early Drosophila embryogenesis. EMBO J. 17:5141-50
136. Orlando V, Paro R. 1993. Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin. Cell 75:1187-98
137. Palacios D, Mozzetta C, Consalvi S, Caretti G, Saccone V, et al. 2010. TNF/p38α/Polycomb signaling to Pax7 locus in satellite cells links inflammation to the epigenetic control of muscle regeneration. Cell Stem Cell 7:455-69
138. Pan G, Tian S, Nie J, Yang C, Ruotti V, et al. 2007. Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells. Cell Stem Cell 1:299-312
139. Papp B, Muller J. 2006. Histone trimethylation and the maintenance of transcriptional ON and OFF states by trxG and PcG proteins. Genes Dev. 20:2041-54
140. Paro R. 1990. Imprinting a determined state into the chromatin of Drosophila. Trends Genet. 6:416-21
141. Paro R, HognessDS. 1991. The Polycomb protein shares a homologous domain with a heterochromatinassociated protein of Drosophila. Proc. Natl. Acad. Sci. USA 88:263-67
142. Pasini D, Bracken AP, Jensen MR, Lazzerini Denchi E, Helin K. 2004. Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity. EMBO J. 23:4061-71
143. Pasini D, Cloos PA, Walfridsson J, Olsson L, Bukowski JP, et al. 2010. JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells. Nature 464:306-10
144. Pasini D, Hansen KH, Christensen J, Agger K, Cloos PA, Helin K. 2008. Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-repressive complex 2. Genes Dev. 22:1345-55
145. Pauli A, Rinn JL, Schier AF. 2011. Non-coding RNAs as regulators of embryogenesis. Nat. Rev. Genet. 12:136-49
146. Peters AH, Kubicek S, Mechtler K, O'Sullivan RJ, Derijck AA, et al. 2003. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol. Cell 12:1577-89
147. Peterson AJ, Mallin DR, Francis NJ, Ketel CS, Stamm J, et al. 2004. Requirement for Sex Comb on Midleg protein interactions in Drosophila Polycomb group repression. Genetics 167:1225-39
148. Petruk S, Sedkov Y, Riley KM, Hodgson J, Schweisguth F, et al. 2006. Transcription of bxd noncoding RNAs promoted by trithorax represses Ubx in cis by transcriptional interference. Cell 127:1209-21
149. Plath K, Fang J, Mlynarczyk-Evans SK, Cao R, Worringer KA, et al. 2003. Role of histone H3 lysine 27 methylation in X inactivation. Science 300:131-35
150. Popov N, Gil J. 2010. Epigenetic regulation of the INK4b-ARF-INK4a locus: in sickness and in health. Epigenetics 5:685-90
151. Posfai E, Kunzmann R, Brochard V, Salvaing J, Cabuy E, et al. 2012. Polycomb function during oogenesis is required for mouse embryonic development. Genes Dev. 26:920-32
152. Rank G, Prestel M, Paro R. 2002. Transcription through intergenic chromosomal memory elements of the Drosophila bithorax complex correlates with an epigenetic switch. Mol. Cell. Biol. 22:8026-34
153. Ren X, Vincenz C, Kerppola TK. 2008. Changes in the distributions and dynamics of Polycomb repressive complexes during embryonic stem cell differentiation. Mol. Cell. Biol. 28:2884-95
154. Reynolds N, Salmon-Divon M, Dvinge H, Hynes-Allen A, Balasooriya G, et al. 2012. NuRD-mediated deacetylation of H3K27 facilitates recruitment of Polycomb repressive complex 2 to direct gene repression. EMBO J. 31:593-605
155. Richly H, Aloia L, Di Croce L. 2011. Roles of the Polycomb group proteins in stem cells and cancer. Cell Death Dis. 2:e204
156. Ringrose L, Paro R. 2007. Polycomb/Trithorax response elements and epigenetic memory of cell identity. Development 134:223-32
157. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, et al. 2007. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311-23
158. Ross JM, Zarkower D. 2003. Polycomb group regulation of Hox gene expression in C. elegans. Dev. Cell 4:891-901
159. Sarma K, Margueron R, Ivanov A, Pirrotta V, Reinberg D. 2008. Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in vivo. Mol. Cell. Biol. 28:2718-31
160. Satijn DP, Hamer KM, den Blaauwen J, Otte AP. 2001. The Polycomb group protein EED interacts with YY1, and both proteins induce neural tissue in Xenopus embryos. Mol. Cell. Biol. 21:1360-69
161. Sato T, Denell RE. 1985. Homoeosis in Drosophila: anterior and posterior transformations of Polycomb lethal embryos. Dev. Biol. 110:53-64
162. Scharf AN, Barth TK, Imhof A. 2009. Establishment of histone modifications after chromatin assembly. Nucleic Acids Res. 37:5032-40
163. Scheuermann JC, de Ayala Alonso AG, Oktaba K, Ly-Hartig N, McGinty RK, et al. 2010. HistoneH2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature 465:243-47
164. Schmitges FW, Prusty AB, Faty M, Stutzer A, Lingaraju GM, et al. 2011. Histonemethylation by PRC2 is inhibited by active chromatin marks. Mol. Cell 42:330-41
165. Schmitt S, Prestel M, Paro R. 2005. Intergenic transcription through a Polycomb group response element counteracts silencing. Genes Dev. 19:697-708
166. Schoeftner S, Sengupta AK, Kubicek S, Mechtler K, Spahn L, et al. 2006. Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. EMBO J. 25:3110-22
167. Schorderet P, Duboule D. 2011. Structural and functional differences in the long non-coding RNA HOTAIR in mouse and human. PLoS Genet. 7:e1002071
168. Schuettengruber B, Ganapathi M, Leblanc B, Portoso M, Jaschek R, et al. 2009. Functional anatomy of Polycomb and trithorax chromatin landscapes in Drosophila embryos. PLoS Biol. 7:e13
169. Schuettengruber B, Martinez AM, Iovino N, Cavalli G. 2011. Trithorax group proteins: switching genes on and keeping them active. Nat. Rev. Mol. Cell Biol. 12:799-814
170. Schumacher A, Magnuson T. 1997. Murine Polycomb- and trithorax-group genes regulate homeotic pathways and beyond. Trends Genet. 13:167-70
171. Schwartz YB, Kahn TG, Nix DA, Li XY, Bourgon R, et al. 2006. Genome-wide analysis of Polycomb targets in Drosophila melanogaster. Nat. Genet. 38:700-5
172. Sessa L, Breiling A, Lavorgna G, Silvestri L, Casari G, Orlando V. 2007. Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster. RNA 13:223-39
173. Sexton T, Yaffe E, Kenigsberg E, Bantignies F, Leblanc B, et al. 2012. Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148:458-72
174. Shao Z, Raible F, Mollaaghababa R, Guyon JR, Wu CT, et al. 1999. Stabilization of chromatin structure by PRC1, a Polycomb complex. Cell 98:37-46
175. Shen X, Liu Y, Hsu YJ, Fujiwara Y, Kim J, et al. 2008. EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol. Cell 32:491-502
176. Simmons Kovacs LA, Mayhew MB, Orlando DA, Jin Y, Li Q, et al. 2012. Cyclin-dependent kinases are regulators and effectors of oscillations driven by a transcription factor network. Mol. Cell 45:669-79
177. Simonis M, Klous P, Splinter E, Moshkin Y, Willemsen R, et al. 2006. Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C). Nat. Genet. 38:1348-54
178. Sing A, Pannell D, Karaiskakis A, Sturgeon K, Djabali M, et al. 2009. A vertebrate Polycomb response element governs segmentation of the posterior hindbrain. Cell 138:885-97
179. Smith M, Mallin DR, Simon JA, Courey AJ. 2011. Small ubiquitin-like modifier (SUMO) conjugation impedes transcriptional silencing by the Polycomb group repressor Sex Comb on Midleg. J. Biol. Chem. 286:11391-400
180. Stock JK, Giadrossi S, Casanova M, Brookes E, Vidal M, et al. 2007. Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells. Nat. Cell Biol. 9:1428-35
181. Stojic L, Jasencakova Z, Prezioso C, Stutzer A, Bodega B, et al. 2011. Chromatin regulated interchange between polycomb repressive complex 2 (PRC2)-Ezh2 and PRC2-Ezh1 complexes controls myogenin activation in skeletal muscle cells. Epigenet. Chromatin 4:16
182. Surface LE, Thornton SR, Boyer LA. 2010. Polycomb group proteins set the stage for early lineage commitment. Cell Stem Cell 7:288-98
183. Sustackova G, Kozubek S, Stixova L, Legartova S, Matula P, et al. 2012. Acetylation-dependent nuclear arrangement and recruitment of BMI1 protein to UV-damaged chromatin. J. Cell Physiol. 227:1838-50
184. Taberlay PC, Kelly TK, Liu CC, You JS, De Carvalho DD, et al. 2011. Polycomb-repressed genes have permissive enhancers that initiate reprogramming. Cell 147:1283-94
185. Takihara Y, Tomotsune D, Shirai M, Katoh-Fukui Y, Nishii K, et al. 1997. Targeted disruption of the mouse homologue of the Drosophila polyhomeotic gene leads to altered anteroposterior patterning and neural crest defects. Development 124:3673-82
186. Tavares L, Dimitrova E, Oxley D, Webster J, Poot R, et al. 2012. RYBP-PRC1 complexes mediateH2A ubiquitylation at Polycomb target sites independently of PRC2 and H3K27me3. Cell 148:664-78
187. Terranova R, Yokobayashi S, Stadler MB, Otte AP, van Lohuizen M, et al. 2008. Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos. Dev. Cell 15:668-79
188. Tie F, Stratton CA, Kurzhals RL, Harte PJ. 2007. The N terminus of Drosophila ESC binds directly to histoneH3 and is required for E(Z)-dependent trimethylation ofH3 lysine 27. Mol. Cell. Biol. 27:2014-26
189. Tiwari VK, McGarvey KM, Licchesi JD, Ohm JE, Herman JG, et al. 2008. PcG proteins, DNA methylation, and gene repression by chromatin looping. PLoS Biol. 6:2911-27
190. Tolhuis B, Blom M, Kerkhoven RM, Pagie L, Teunissen H, et al. 2011. Interactions among Polycomb domains are guided by chromosome architecture. PLoS Genet. 7:e1001343
191. Tolhuis B, Muijrers I, deWit E, TeunissenH, Talhout W, et al. 2006. Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster. Nat. Genet. 38:694-99
192. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, et al. 2010. Long noncodingRNAasmodular scaffold of histone modification complexes. Science 329:689-93
193. Vazquez J, Muller M, Pirrotta V, Sedat JW. 2006. The Mcp element mediates stable long-range chromosome-chromosome interactions in Drosophila. Mol. Biol. Cell 17:2158-65
194. Vella P, Barozzi I, CuomoA, BonaldiT, PasiniD. 2011. YinYang 1 extends theMyc-related transcription factors network in embryonic stem cells. Nucleic Acids Res. 40:3403-18
195. Voncken JW, Roelen BA, Roefs M, de Vries S, Verhoeven E, et al. 2003. Rnf2 (Ring1b) deficiency causes gastrulation arrest and cell cycle inhibition. Proc. Natl. Acad. Sci. USA 100:2468-73
196. Walker E, Chang WY, Hunkapiller J, Cagney G, Garcha K, et al. 2010. Polycomb-like 2 associates with PRC2 and regulates transcriptional networks during mouse embryonic stem cell self-renewal and differentiation. Cell Stem Cell 6:153-66
197. Wang H, Wang L, Erdjument-Bromage H, Vidal M, Tempst P, et al. 2004. Role of histone H2A ubiquitination in Polycomb silencing. Nature 431:873-78
198. Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, et al. 2011. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472:120-24
199. Wang L, Brown JL, Cao R, Zhang Y, Kassis JA, Jones RS. 2004. Hierarchical recruitment of Polycomb group silencing complexes. Mol. Cell 14:637-46
200. Wang L, Jahren N, Miller EL, KetelCS, Mallin DR, Simon JA. 2010. Comparative analysis of chromatin binding by sex comb on midleg (SCM) and other polycomb group repressors at a Drosophila Hox gene. Mol. Cell. Biol. 30:2584-93
201. Wei Y, Chen YH, Li LY, Lang J, Yeh SP, et al. 2011. CDK1-dependent phosphorylation of EZH2 suppresses methylation ofH3K27 and promotes osteogenic differentiation of human mesenchymal stem cells. Nat. Cell Biol. 13:87-94
202. Weintraub H, Worcel A, Alberts B. 1976. A model for chromatin based upon two symmetrically paired half-nucleosomes. Cell 9:409-17
203. Whitcomb SJ, Basu A, Allis CD, Bernstein E. 2007. Polycomb group proteins: an evolutionary perspective. Trends Genet. 23:494-502
204. Wilkinson F, Pratt H, Atchison ML. 2010. PcG recruitment by the YY1 REPO domain can be mediated by Yaf2. J. Cell Biochem. 109:478-86
205. Woo CJ, Kharchenko PV, Daheron L, Park PJ, Kingston RE. 2010. A region of the human HOXD cluster that confers Polycomb-group responsiveness. Cell 140:99-110
206. Wu S, Shi Y, Mulligan P, Gay F, Landry J, et al. 2007. A YY1-INO80 complex regulates genomic stability through homologous recombination-based repair. Nat. Struct. Mol. Biol. 14:1165-72
207. Wu SC, Zhang Y. 2011. Cyclin-dependent kinase 1 (CDK1)-mediated phosphorylation of enhancer of zeste 2 (Ezh2) regulates its stability. J. Biol. Chem. 286:28511-19
208. Xi H, Yu Y, Fu Y, Foley J, Halees A, Weng Z. 2007. Analysis of overrepresented motifs in human core promoters reveals dual regulatory roles of YY1. Genome Res. 17:798-806
209. Xu M, Long C, Chen X, Huang C, Chen S, Zhu B. 2010. Partitioning of histone H3-H4 tetramers during DNA replication-dependent chromatin assembly. Science 328:94-98
210. Xu M, Wang W, Chen S, Zhu B. 2011. A model for mitotic inheritance of histone lysine methylation. EMBO Rep. 13:60-67
211. Yaffe E, Tanay A. 2011. Probabilistic modeling of Hi-C contact maps eliminates systematic biases to characterize global chromosomal architecture. Nat. Genet. 43:1059-65
212. Yamasu K, Senshu T. 1990. Conservative segregation of tetrameric units of H3 and H4 histones during nucleosome replication. J. Biochem. 107:15-20
213. Yang L, Lin C, Liu W, Zhang J, Ohgi KA, et al. 2011. ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell 147:773-88
214. Yap KL, Li S, Munoz-Cabello AM, Raguz S, Zeng L, et al. 2010. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by Polycomb CBX7 in transcriptional silencing of INK4a. Mol. Cell 38:662-74
215. Yu M, Mazor T, Huang H, Huang HT, Kathrein KL, et al. 2012. Direct recruitment of Polycomb repressive complex 1 to chromatin by core binding transcription factors. Mol. Cell 45:330-43
216. YuanW, Xu M, HuangC, Liu N, Chen S, ZhuB. 2011.H3K36methylation antagonizes PRC2-mediated H3K27 methylation. J. Biol. Chem. 286:7983-89
217. Zaaroor-RegevD, de Bie P, ScheffnerM, Noy T, Shemer R, et al. 2010. Regulation of the Polycomb protein Ring1B by self-ubiquitination or by E6-AP may have implications to the pathogenesis of Angelman syndrome. Proc. Natl. Acad. Sci. USA 107:6788-93
218. Zhao J, Ohsumi TK, Kung JT, Ogawa Y, Grau DJ, et al. 2010. Genome-wide identification of Polycombassociated RNAs by RIP-seq. Mol. Cell 40:939-53
219. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. 2008. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322:750-56
220. Zink B, Paro R. 1989. In vivo binding pattern of a trans-regulator of homoeotic genes in Drosophila melanogaster. Nature 337:468-71