1932

Abstract

Predicting regulatory potential from primary DNA sequences or transcription factor binding patterns is not possible. However, the annotation of the genome by chromatin proteins, histone modifications, and differential compaction is largely sufficient to reveal the locations of genes and their differential activity states. The Polycomb Group (PcG) and Trithorax Group (TrxG) proteins are the central players in this cell type–specific chromatin organization. PcG function was originally viewed as being solely repressive and irreversible, as observed at the homeotic loci in flies and mammals. However, it is now clear that modular and reversible PcG function is essential at most developmental genes. Focusing mainly on recent advances, we review evidence for how PcG and TrxG patterns change dynamically during cell type transitions. The ability to implement cell type–specific transcriptional programming with exquisite fidelity is essential for normal development.

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2020-06-20
2024-04-25
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Literature Cited

  1. 1. 
    Laugesen A, Hojfeldt JW, Helin K 2019. Molecular mechanisms directing PRC2 recruitment and H3K27 methylation. Mol. Cell 74:8–18
    [Google Scholar]
  2. 2. 
    Vidal M. 2019. Polycomb assemblies multitask to regulate transcription. Epigenomes 3:12
    [Google Scholar]
  3. 3. 
    Yu JR, Lee CH, Oksuz O, Stafford JM, Reinberg D 2019. PRC2 is high maintenance. Genes Dev 33:903–35
    [Google Scholar]
  4. 4. 
    Holoch D, Margueron R. 2017. Mechanisms regulating PRC2 recruitment and enzymatic activity. Trends Biochem. Sci. 42:531–42
    [Google Scholar]
  5. 5. 
    Schuettengruber B, Bourbon HM, Di Croce L, Cavalli G 2017. Genome regulation by Polycomb and Trithorax: 70 years and counting. Cell 171:34–57
    [Google Scholar]
  6. 6. 
    Lewis EB. 1978. A gene complex controlling segmentation in Drosophila. Nature 276:565–70
    [Google Scholar]
  7. 7. 
    Struhl G. 1981. A gene product required for correct initiation of segmental determination in Drosophila. Nature 293:36–41
    [Google Scholar]
  8. 8. 
    Ingham PW. 1983. Differential expression of bithorax complex genes in the absence of the extra sex combs and trithorax genes. Nature 306:591–93
    [Google Scholar]
  9. 9. 
    Pasini D, Di Croce L 2016. Emerging roles for Polycomb proteins in cancer. Curr. Opin. Genet. Dev. 36:50–58
    [Google Scholar]
  10. 10. 
    Poynter ST, Kadoch C. 2016. Polycomb and trithorax opposition in development and disease. WIREs Dev. Biol. 5:659–88
    [Google Scholar]
  11. 11. 
    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
    [Google Scholar]
  12. 12. 
    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
    [Google Scholar]
  13. 13. 
    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
    [Google Scholar]
  14. 14. 
    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
    [Google Scholar]
  15. 15. 
    Czermin B, Melfi R, McCabe D, Seitz V, Imhof A, Pirrotta V 2002. Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell 111:185–96
    [Google Scholar]
  16. 16. 
    Muller J, Hart CM, Francis NJ, Vargas ML, Sengupta A et al. 2002. Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell 111:197–208
    [Google Scholar]
  17. 17. 
    Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D 2002. Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev 16:2893–905
    [Google Scholar]
  18. 18. 
    Pengelly AR, Copur O, Jackle H, Herzig A, Muller J 2013. A histone mutant reproduces the phenotype caused by loss of histone-modifying factor Polycomb. Science 339:698–99
    [Google Scholar]
  19. 19. 
    Pengelly AR, Kalb R, Finkl K, Muller J 2015. Transcriptional repression by PRC1 in the absence of H2A monoubiquitylation. Genes Dev 29:1487–92
    [Google Scholar]
  20. 20. 
    Blackledge NP, Fursova NA, Kelley JR, Huseyin MK, Feldmann A, Klose RJ 2019. PRC1 catalytic activity is central to Polycomb system function. bioRxiv 667667. https://doi.org/10.1101/667667
    [Crossref]
  21. 21. 
    Tamburri S, Lavarone E, Fernandez-Perez D, Zanotti M, Manganaro D et al. 2019. Histone H2AK119 mono-ubiquitination is essential for Polycomb-mediated transcriptional repression. bioRxiv 690461. https://doi.org/10.1101/690461
    [Crossref]
  22. 22. 
    Piunti A, Shilatifard A. 2016. Epigenetic balance of gene expression by Polycomb and COMPASS families. Science 352:aad9780
    [Google Scholar]
  23. 23. 
    Schmähling S, Meiler A, Lee Y, Mohammed A, Finkl K et al. 2018. Regulation and function of H3K36 di-methylation by the trithorax-group protein complex AMC. Development 145:dev163808
    [Google Scholar]
  24. 24. 
    Huang C, Yang F, Zhang Z, Zhang J, Cai G et al. 2017. Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila. Nat. Commun 8:1649
    [Google Scholar]
  25. 25. 
    Wang L, Joshi P, Miller EL, Higgins L, Slattery M, Simon JA 2018. A role for monomethylation of histone H3-K27 in gene activity in Drosophila. Genetics 208:1023–36
    [Google Scholar]
  26. 26. 
    Lee HG, Kahn TG, Simcox A, Schwartz YB, Pirrotta V 2015. Genome-wide activities of Polycomb complexes control pervasive transcription. Genome Res 25:1170–81
    [Google Scholar]
  27. 27. 
    Ferrari KJ, Scelfo A, Jammula S, Cuomo A, Barozzi I et al. 2014. Polycomb-dependent H3K27me1 and H3K27me2 regulate active transcription and enhancer fidelity. Mol. Cell 53:49–62
    [Google Scholar]
  28. 28. 
    Schaaf CA, Misulovin Z, Gause M, Koenig A, Gohara DW et al. 2013. Cohesin and polycomb proteins functionally interact to control transcription at silenced and active genes. PLOS Genet 9:e1003560
    [Google Scholar]
  29. 29. 
    Gao Z, Lee P, Stafford JM, von Schimmelmann M, Schaefer A, Reinberg D 2014. An AUTS2-Polycomb complex activates gene expression in the CNS. Nature 516:349–54
    [Google Scholar]
  30. 30. 
    Creppe C, Palau A, Malinverni R, Valero V, Buschbeck M 2014. A Cbx8-containing Polycomb complex facilitates the transition to gene activation during ES cell differentiation. PLOS Genet 10:e1004851
    [Google Scholar]
  31. 31. 
    Kloet SL, Makowski MM, Baymaz HI, van Voorthuijsen L, Karemaker ID et al. 2016. The dynamic interactome and genomic targets of Polycomb complexes during stem-cell differentiation. Nat. Struct. Mol. Biol. 23:682–90
    [Google Scholar]
  32. 32. 
    Loubiere V, Delest A, Thomas A, Bonev B, Schuettengruber B et al. 2016. Coordinate redeployment of PRC1 proteins suppresses tumor formation during Drosophila development. Nat. Genet. 48:1436–42
    [Google Scholar]
  33. 33. 
    Pemberton H, Anderton E, Patel H, Brookes S, Chandler H et al. 2014. Genome-wide co-localization of Polycomb orthologs and their effects on gene expression in human fibroblasts. Genome Biol 15:R23
    [Google Scholar]
  34. 34. 
    van den Boom V, Maat H, Geugien M, Rodriguez Lopez A, Sotoca AM et al. 2016. Non-canonical PRC1.1 targets active genes independent of H3K27me3 and is essential for leukemogenesis. Cell Rep 14:332–46
    [Google Scholar]
  35. 35. 
    Brown JL, Sun MA, Kassis JA 2018. Global changes of H3K27me3 domains and Polycomb group protein distribution in the absence of recruiters Spps or Pho. PNAS 115:E1839–48
    [Google Scholar]
  36. 36. 
    Pherson M, Misulovin Z, Gause M, Mihindukulasuriya K, Swain A, Dorsett D 2017. Polycomb repressive complex 1 modifies transcription of active genes. Sci. Adv. 3:e1700944
    [Google Scholar]
  37. 37. 
    Cohen I, Zhao D, Bar C, Valdes VJ, Dauber-Decker KL et al. 2018. PRC1 fine-tunes gene repression and activation to safeguard skin development and stem cell specification. Cell Stem Cell 22:726–39.e7
    [Google Scholar]
  38. 38. 
    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
    [Google Scholar]
  39. 39. 
    De Cegli R, Iacobacci S, Flore G, Gambardella G, Mao L et al. 2013. Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation. Nucleic Acids Res 41:711–26
    [Google Scholar]
  40. 40. 
    Smits AH, Jansen PW, Poser I, Hyman AA, Vermeulen M 2013. Stoichiometry of chromatin-associated protein complexes revealed by label-free quantitative mass spectrometry-based proteomics. Nucleic Acids Res 41:e28
    [Google Scholar]
  41. 41. 
    Alekseyenko AA, Gorchakov AA, Kharchenko PV, Kuroda MI 2014. Reciprocal interactions of human C10orf12 and C17orf96 with PRC2 revealed by BioTAP-XL cross-linking and affinity purification. PNAS 111:2488–93
    [Google Scholar]
  42. 42. 
    Liefke R, Shi Y. 2015. The PRC2-associated factor C17orf96 is a novel CpG island regulator in mouse ES cells. Cell Discov 1:15008
    [Google Scholar]
  43. 43. 
    Beringer M, Pisano P, Di Carlo V, Blanco E, Chammas P et al. 2016. EPOP functionally links Elongin and Polycomb in pluripotent stem cells. Mol. Cell 64:645–58
    [Google Scholar]
  44. 44. 
    Liefke R, Karwacki-Neisius V, Shi Y 2016. EPOP interacts with Elongin BC and USP7 to modulate the chromatin landscape. Mol. Cell 64:65972 Erratum 2017.Mol. Cell 65:202
    [Google Scholar]
  45. 45. 
    Conway E, Jerman E, Healy E, Ito S, Holoch D et al. 2018. A family of vertebrate-specific Polycombs encoded by the LCOR/LCORL genes balance PRC2 subtype activities. Mol. Cell 70:408–21.e8
    [Google Scholar]
  46. 46. 
    Lee CH, Holder M, Grau D, Saldana-Meyer R, Yu JR et al. 2018. Distinct stimulatory mechanisms regulate the catalytic activity of polycomb repressive complex 2. Mol. Cell 70:435–48.e5
    [Google Scholar]
  47. 47. 
    Fursova NA, Blackledge NP, Nakayama M, Ito S, Koseki Y et al. 2019. Synergy between variant PRC1 complexes defines Polycomb-mediated gene repression. Mol. Cell 74:1020–36.e8
    [Google Scholar]
  48. 48. 
    Arrigoni R, Alam SL, Wamstad JA, Bardwell VJ, Sundquist WI, Schreiber-Agus N 2006. The Polycomb-associated protein Rybp is a ubiquitin binding protein. FEBS Lett 580:6233–41
    [Google Scholar]
  49. 49. 
    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
    [Google Scholar]
  50. 50. 
    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
    [Google Scholar]
  51. 51. 
    Oksuz O, Narendra V, Lee CH, Descostes N, LeRoy G et al. 2018. Capturing the onset of PRC2-mediated repressive domain formation. Mol. Cell 70:1149–62.e5
    [Google Scholar]
  52. 52. 
    Cooper S, Grijzenhout A, Underwood E, Ancelin K, Zhang T et al. 2016. Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2. Nat. Commun. 7:13661
    [Google Scholar]
  53. 53. 
    Kalb R, Latwiel S, Baymaz HI, Jansen PW, Muller CW et al. 2014. Histone H2A monoubiquitination promotes histone H3 methylation in Polycomb repression. Nat. Struct. Mol. Biol. 21:569–71
    [Google Scholar]
  54. 54. 
    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
    [Google Scholar]
  55. 55. 
    Kasinath V, Faini M, Poepsel S, Reif D, Feng XA et al. 2018. Structures of human PRC2 with its cofactors AEBP2 and JARID2. Science 359:940–44
    [Google Scholar]
  56. 56. 
    Chen S, Jiao L, Shubbar M, Yang X, Liu X 2018. Unique structural platforms of Suz12 dictate distinct classes of PRC2 for chromatin binding. Mol. Cell 69:840–52.e5
    [Google Scholar]
  57. 57. 
    Chittock EC, Latwiel S, Miller TC, Muller CW 2017. Molecular architecture of polycomb repressive complexes. Biochem. Soc. Trans. 45:193–205
    [Google Scholar]
  58. 58. 
    Vann KR, Kutateladze TG. 2018. Architecture of PRC2 holo complexes. Trends Biochem. Sci. 43:487–89
    [Google Scholar]
  59. 59. 
    Kasinath V, Poepsel S, Nogales E 2019. Recent structural insights into Polycomb repressive complex 2 regulation and substrate binding. Biochemistry 58:346–54
    [Google Scholar]
  60. 60. 
    McGinty RK, Henrici RC, Tan S 2014. Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome. Nature 514:591–96
    [Google Scholar]
  61. 61. 
    Kassis JA. 2002. Pairing-sensitive silencing, Polycomb group response elements, and transposon homing in Drosophila. Adv. Genet. 46:421–38
    [Google Scholar]
  62. 62. 
    Ringrose L, Paro R. 2004. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu. Rev. Genet. 38:413–43
    [Google Scholar]
  63. 63. 
    Kassis JA, Brown JL. 2013. Polycomb group response elements in Drosophila and vertebrates. Adv. Genet. 81:83–118
    [Google Scholar]
  64. 64. 
    Americo J, Whiteley M, Brown JL, Fujioka M, Jaynes JB, Kassis JA 2002. A complex array of DNA-binding proteins required for pairing-sensitive silencing by a Polycomb group response element from the Drosophila engrailed gene. Genetics 160:1561–71
    [Google Scholar]
  65. 65. 
    Brown JL, Mucci D, Whiteley M, Dirksen ML, Kassis JA 1998. The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein with homology to the transcription factor YY1. Mol. Cell 1:1057–64
    [Google Scholar]
  66. 66. 
    Klymenko T, Papp B, Fischle W, Kocher T, Schelder M et al. 2006. A Polycomb group protein complex with sequence-specific DNA-binding and selective methyl-lysine-binding activities. Genes Dev 20:1110–22
    [Google Scholar]
  67. 67. 
    Frey F, Sheahan T, Finkl K, Stoehr G, Mann M et al. 2016. Molecular basis of PRC1 targeting to Polycomb response elements by PhoRC. Genes Dev 30:1116–27
    [Google Scholar]
  68. 68. 
    Kahn TG, Dorafshan E, Schultheis D, Zare A, Stenberg P et al. 2016. Interdependence of PRC1 and PRC2 for recruitment to Polycomb Response Elements. Nucleic Acids Res 44:10132–49
    [Google Scholar]
  69. 69. 
    Kang H, McElroy KA, Jung YL, Alekseyenko AA, Zee BM et al. 2015. Sex comb on midleg (Scm) is a functional link between PcG-repressive complexes in Drosophila. Genes Dev 29:1136–50
    [Google Scholar]
  70. 70. 
    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
    [Google Scholar]
  71. 71. 
    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
    [Google Scholar]
  72. 72. 
    Woo CJ, Kharchenko PV, Daheron L, Park PJ, Kingston RE 2013. Variable requirements for DNA-binding proteins at Polycomb-dependent repressive regions in human HOX clusters. Mol. Cell. Biol. 33:3274–85
    [Google Scholar]
  73. 73. 
    Schorderet P, Lonfat N, Darbellay F, Tschopp P, Gitto S et al. 2013. A genetic approach to the recruitment of PRC2 at the HoxD locus. PLOS Genet 9:e1003951
    [Google Scholar]
  74. 74. 
    Fujioka M, Sun G, Jaynes JB 2013. The Drosophila eve insulator Homie promotes eve expression and protects the adjacent gene from repression by Polycomb spreading. PLOS Genet 9:e1003883
    [Google Scholar]
  75. 75. 
    Narendra V, Rocha PP, An D, Raviram R, Skok JA et al. 2015. CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation. Science 347:1017–21
    [Google Scholar]
  76. 76. 
    Hnisz D, Weintraub AS, Day DS, Valton AL, Bak RO et al. 2016. Activation of proto-oncogenes by disruption of chromosome neighborhoods. Science 351:1454–58
    [Google Scholar]
  77. 77. 
    De S, Cheng Y, Sun MA, Gehred ND, Kassis JA 2019. Structure and function of an ectopic Polycomb chromatin domain. Sci. Adv. 5:eaau9739
    [Google Scholar]
  78. 78. 
    Schmitges FW, Prusty AB, Faty M, Stutzer A, Lingaraju GM et al. 2011. Histone methylation by PRC2 is inhibited by active chromatin marks. Mol. Cell 42:330–41
    [Google Scholar]
  79. 79. 
    Li XY, Harrison MM, Villalta JE, Kaplan T, Eisen MB 2014. Establishment of regions of genomic activity during the Drosophila maternal to zygotic transition. eLife 3:e03737
    [Google Scholar]
  80. 80. 
    Zenk F, Loeser E, Schiavo R, Kilpert F, Bogdanovic O, Iovino N 2017. Germ line–inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition. Science 357:212–16
    [Google Scholar]
  81. 81. 
    Hojfeldt JW, Laugesen A, Willumsen BM, Damhofer H, Hedehus L et al. 2018. Accurate H3K27 methylation can be established de novo by SUZ12-directed PRC2. Nat. Struct. Mol. Biol. 25:225–32
    [Google Scholar]
  82. 82. 
    De S, Mitra A, Cheng Y, Pfeifer K, Kassis JA 2016. Formation of a Polycomb-domain in the absence of strong Polycomb response elements. PLOS Genet 12:e1006200
    [Google Scholar]
  83. 83. 
    Peng JC, Valouev A, Swigut T, Zhang J, Zhao Y et al. 2009. Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells. Cell 139:1290–302
    [Google Scholar]
  84. 84. 
    Li H, Liefke R, Jiang J, Kurland JV, Tian W et al. 2017. Polycomb-like proteins link the PRC2 complex to CpG islands. Nature 549:287–91
    [Google Scholar]
  85. 85. 
    Poepsel S, Kasinath V, Nogales E 2018. Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes. Nat. Struct. Mol. Biol. 25:154–62
    [Google Scholar]
  86. 86. 
    Ogiyama Y, Schuettengruber B, Papadopoulos GL, Chang JM, Cavalli G 2018. Polycomb-dependent chromatin looping contributes to gene silencing during Drosophila development. Mol. Cell 71:73–88.e5
    [Google Scholar]
  87. 87. 
    Robinson AK, Leal BZ, Chadwell LV, Wang R, Ilangovan U et al. 2012. The growth-suppressive function of the Polycomb Group protein polyhomeotic is mediated by polymerization of its Sterile Alpha Motif (SAM) domain. J. Biol. Chem. 287:8702–13
    [Google Scholar]
  88. 88. 
    Plys AJ, Davis CP, Kim J, Rizki G, Keenen MM et al. 2019. Phase separation of Polycomb-repressive complex 1 is governed by a charged disordered region of CBX2. Genes Dev 33:799–813
    [Google Scholar]
  89. 89. 
    Zylicz JJ, Bousard A, Zumer K, Dossin F, Mohammad E et al. 2019. The implication of early chromatin changes in X chromosome inactivation. Cell 176:182–97.e23
    [Google Scholar]
  90. 90. 
    Eissenberg JC, Elgin SC. 2014. HP1a: a structural chromosomal protein regulating transcription. Trends Genet 30:103–10
    [Google Scholar]
  91. 91. 
    Ferrari F, Alekseyenko AA, Park PJ, Kuroda MI 2014. Transcriptional control of a whole chromosome: emerging models for dosage compensation. Nat. Struct. Mol. Biol. 21:118–25
    [Google Scholar]
  92. 92. 
    Kondo T, Ito S, Koseki H 2016. Polycomb in transcriptional phase transition of developmental genes. Trends Biochem. Sci. 41:9–19
    [Google Scholar]
  93. 93. 
    Marasca F, Bodega B, Orlando V 2018. How Polycomb-mediated cell memory deals with a changing environment: variations in PcG complexes and proteins assortment convey plasticity to epigenetic regulation as a response to environment. Bioessays 40:e1700137
    [Google Scholar]
  94. 94. 
    Blackledge NP, Rose NR, Klose RJ 2015. Targeting Polycomb systems to regulate gene expression: modifications to a complex story. Nat. Rev. Mol. Cell Biol. 16:643–49
    [Google Scholar]
  95. 95. 
    Klose RJ, Cooper S, Farcas AM, Blackledge NP, Brockdorff N 2013. Chromatin sampling—an emerging perspective on targeting Polycomb repressor proteins. PLOS Genet 9:e1003717
    [Google Scholar]
  96. 96. 
    Lynch MD, Smith AJ, De Gobbi M, Flenley M, Hughes JR et al. 2012. An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment. EMBO J 31:317–29
    [Google Scholar]
  97. 97. 
    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
    [Google Scholar]
  98. 98. 
    Wachter E, Quante T, Merusi C, Arczewska A, Stewart F et al. 2014. Synthetic CpG islands reveal DNA sequence determinants of chromatin structure. eLife 3:e03397
    [Google Scholar]
  99. 99. 
    Jermann P, Hoerner L, Burger L, Schubeler D 2014. Short sequences can efficiently recruit histone H3 lysine 27 trimethylation in the absence of enhancer activity and DNA methylation. PNAS 111:E3415–21
    [Google Scholar]
  100. 100. 
    Pirrotta V. 1997. PcG complexes and chromatin silencing. Curr. Opin. Genet. Dev. 7:249–58
    [Google Scholar]
  101. 101. 
    Paro R. 1995. Propagating memory of transcriptional states. Trends Genet 11:295–97
    [Google Scholar]
  102. 102. 
    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
    [Google Scholar]
  103. 103. 
    Azuara V, Perry P, Sauer S, Spivakov M, Jorgensen HF et al. 2006. Chromatin signatures of pluripotent cell lines. Nat. Cell Biol. 8:532–38
    [Google Scholar]
  104. 104. 
    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
    [Google Scholar]
  105. 105. 
    Shema E, Jones D, Shoresh N, Donohue L, Ram O, Bernstein BE 2016. Single-molecule decoding of combinatorially modified nucleosomes. Science 352:717–21
    [Google Scholar]
  106. 106. 
    Voigt P, LeRoy G, Drury WJ III, Zee BM, Son J et al. 2012. Asymmetrically modified nucleosomes. Cell 151:181–93
    [Google Scholar]
  107. 107. 
    Vastenhouw NL, Schier AF. 2012. Bivalent histone modifications in early embryogenesis. Curr. Opin. Cell Biol. 24:374–86
    [Google Scholar]
  108. 108. 
    Voigt P, Tee WW, Reinberg D 2013. A double take on bivalent promoters. Genes Dev 27:1318–38
    [Google Scholar]
  109. 109. 
    Kang H, Jung YL, McElroy KA, Zee BM, Wallace HA et al. 2017. Bivalent complexes of PRC1 with orthologs of BRD4 and MOZ/MORF target developmental genes in Drosophila. Genes Dev 31:1988–2002
    [Google Scholar]
  110. 110. 
    Akmammedov A, Geigges M, Paro R 2019. Bivalency in Drosophila embryos is associated with strong inducibility of Polycomb target genes. Fly 13:4250
    [Google Scholar]
  111. 111. 
    Schertel C, Albarca M, Rockel-Bauer C, Kelley NW, Bischof J et al. 2015. A large-scale, in vivo transcription factor screen defines bivalent chromatin as a key property of regulatory factors mediating Drosophila wing development. Genome Res 25:514–23
    [Google Scholar]
  112. 112. 
    Rickels R, Hu D, Collings CK, Woodfin AR, Piunti A et al. 2016. An evolutionary conserved epigenetic mark of Polycomb response elements implemented by Trx/MLL/COMPASS. Mol. Cell 63:318–28
    [Google Scholar]
  113. 113. 
    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
    [Google Scholar]
  114. 114. 
    Kassis JA, Kennison JA, Tamkun JW 2017. Polycomb and Trithorax group genes in Drosophila. Genetics 206:1699–725
    [Google Scholar]
  115. 115. 
    Cohen I, Zhao D, Menon G, Nakayama M, Koseki H et al. 2019. PRC1 preserves epidermal tissue integrity independently of PRC2. Genes Dev 33:55–60
    [Google Scholar]
  116. 116. 
    Wang D, Yi R. 2019. Is it time to take R(epressive) out of PRC1. Genes Dev 33:4–5
    [Google Scholar]
  117. 117. 
    Strubbe G, Popp C, Schmidt A, Pauli A, Ringrose L et al. 2011. Polycomb purification by in vivo biotinylation tagging reveals cohesin and Trithorax group proteins as interaction partners. PNAS 108:5572–77
    [Google Scholar]
  118. 118. 
    Digan ME, Haynes SR, Mozer BA, Dawid IB, Forquignon F, Gans M 1986. Genetic and molecular analysis of fs(1)h, a maternal effect homeotic gene in Drosophila. Dev. Biol 114:161–69
    [Google Scholar]
  119. 119. 
    Laue K, Daujat S, Crump JG, Plaster N, Roehl HH et al. 2008. The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity. Development 135:1935–46
    [Google Scholar]
  120. 120. 
    Sheikh BN, Downer NL, Phipson B, Vanyai HK, Kueh AJ et al. 2015. MOZ and BMI1 play opposing roles during Hox gene activation in ES cells and in body segment identity specification in vivo. PNAS 112:5437–42
    [Google Scholar]
  121. 121. 
    Poux S, Horard B, Sigrist CJ, Pirrotta V 2002. The Drosophila Trithorax protein is a coactivator required to prevent re-establishment of Polycomb silencing. Development 129:2483–93
    [Google Scholar]
  122. 122. 
    Kockmann T, Gerstung M, Schlumpf T, Xhinzhou Z, Hess D et al. 2013. The BET protein FSH functionally interacts with ASH1 to orchestrate global gene activity in Drosophila. Genome Biol 14:R18
    [Google Scholar]
  123. 123. 
    Erceg J, Pakozdi T, Marco-Ferreres R, Ghavi-Helm Y, Girardot C et al. 2017. Dual functionality of cis-regulatory elements as developmental enhancers and Polycomb response elements. Genes Dev 31:590–602
    [Google Scholar]
  124. 124. 
    Chinwalla V, Jane EP, Harte PJ 1995. The Drosophila trithorax protein binds to specific chromosomal sites and is co-localized with Polycomb at many sites. EMBO J 14:2056–65
    [Google Scholar]
  125. 125. 
    Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR 2009. Distinctive chromatin in human sperm packages genes for embryo development. Nature 460:473–78
    [Google Scholar]
  126. 126. 
    Lesch BJ, Dokshin GA, Young RA, McCarrey JR, Page DC 2013. A set of genes critical to development is epigenetically poised in mouse germ cells from fetal stages through completion of meiosis. PNAS 110:16061–66
    [Google Scholar]
  127. 127. 
    Sachs M, Onodera C, Blaschke K, Ebata KT, Song JS, Ramalho-Santos M 2013. Bivalent chromatin marks developmental regulatory genes in the mouse embryonic germline in vivo. Cell Rep 3:1777–84
    [Google Scholar]
  128. 128. 
    Hanna CW, Taudt A, Huang J, Gahurova L, Kranz A et al. 2018. MLL2 conveys transcription-independent H3K4 trimethylation in oocytes. Nat. Struct. Mol. Biol. 25:73–82
    [Google Scholar]
  129. 129. 
    Wu SF, Zhang H, Cairns BR 2011. Genes for embryo development are packaged in blocks of multivalent chromatin in zebrafish sperm. Genome Res 21:578–89
    [Google Scholar]
  130. 130. 
    Weaver TM, Liu J, Connelly KE, Coble C, Varzavand K et al. 2019. The EZH2 SANT1 domain is a histone reader providing sensitivity to the modification state of the H4 tail. Sci. Rep. 9:987
    [Google Scholar]
  131. 131. 
    Tie F, Banerjee R, Stratton CA, Prasad-Sinha J, Stepanik V et al. 2009. CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development 136:3131–41
    [Google Scholar]
  132. 132. 
    Blackledge NP, Farcas AM, Kondo T, King HW, McGouran JF et al. 2014. Variant PRC1 complex-dependent H2A ubiquitylation drives PRC2 recruitment and Polycomb domain formation. Cell 157:1445–59
    [Google Scholar]
  133. 133. 
    Dorighi KM, Tamkun JW. 2013. The trithorax group proteins Kismet and ASH1 promote H3K36 dimethylation to counteract Polycomb group repression in Drosophila. Development 140:4182–92
    [Google Scholar]
  134. 134. 
    Denissov S, Hofemeister H, Marks H, Kranz A, Ciotta G et al. 2014. Mll2 is required for H3K4 trimethylation on bivalent promoters in embryonic stem cells, whereas Mll1 is redundant. Development 141:526–37
    [Google Scholar]
  135. 135. 
    Dorafshan E, Kahn TG, Glotov A, Savitsky M, Walther M et al. 2019. Ash1 counteracts Polycomb repression independent of histone H3 lysine 36 methylation. EMBO Rep 20:e46762
    [Google Scholar]
  136. 136. 
    Bracken AP, Brien GL, Verrijzer CP 2019. Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer. Genes Dev 33:93659
    [Google Scholar]
  137. 137. 
    Brand M, Nakka K, Zhu J, Dilworth FJ 2019. Polycomb/Trithorax antagonism: cellular memory in stem cell fate and function. Cell Stem Cell 24:518–33
    [Google Scholar]
  138. 138. 
    Beuchle D, Struhl G, Muller J 2001. Polycomb group proteins and heritable silencing of Drosophila Hox genes. Development 128:993–1004
    [Google Scholar]
  139. 139. 
    Jadhav U, Nalapareddy K, Saxena M, O'Neill NK, Pinello L et al. 2016. Acquired tissue-specific promoter bivalency is a basis for PRC2 necessity in adult cells. Cell 165:1389–400
    [Google Scholar]
  140. 140. 
    Weiner A, Lara-Astiaso D, Krupalnik V, Gafni O, David E et al. 2016. Co-ChIP enables genome-wide mapping of histone mark co-occurrence at single-molecule resolution. Nat. Biotechnol. 34:953–61
    [Google Scholar]
  141. 141. 
    Jadhav U, Cavazza A, Banerjee KK, Xie H, O'Neill NK et al. 2019. Extensive recovery of embryonic enhancer and gene memory stored in hypomethylated enhancer DNA. Mol. Cell 74:542–54.e5
    [Google Scholar]
  142. 142. 
    Pasini D, Malatesta M, Jung HR, Walfridsson J, Willer A et al. 2010. Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes. Nucleic Acids Res 38:4958–69
    [Google Scholar]
  143. 143. 
    Kehle J, Beuchle D, Treuheit S, Christen B, Kennison JA et al. 1998. dMi-2, a Hunchback-interacting protein that functions in Polycomb repression. Science 282:1897–900
    [Google Scholar]
  144. 144. 
    Kim HS, Tan Y, Ma W, Merkurjev D, Destici E et al. 2018. Pluripotency factors functionally premark cell-type-restricted enhancers in ES cells. Nature 556:510–14
    [Google Scholar]
  145. 145. 
    Sadasivam DA, Huang DH. 2018. Feedback regulation by antagonistic epigenetic factors potentially maintains developmental homeostasis in Drosophila. J. Cell Sci 131:jcs210179
    [Google Scholar]
  146. 146. 
    Zink D, Paro R. 1995. Drosophila Polycomb-group regulated chromatin inhibits the accessibility of a trans-activator to its target DNA. EMBO J 14:5660–71
    [Google Scholar]
  147. 147. 
    Fitzgerald DP, Bender W. 2001. Polycomb group repression reduces DNA accessibility. Mol. Cell. Biol. 21:6585–97
    [Google Scholar]
  148. 148. 
    Boettiger AN, Bintu B, Moffitt JR, Wang S, Beliveau BJ et al. 2016. Super-resolution imaging reveals distinct chromatin folding for different epigenetic states. Nature 529:418–22
    [Google Scholar]
  149. 149. 
    Mateo LJ, Murphy SE, Hafner A, Cinquini IS, Walker CA, Boettiger AN 2019. Visualizing DNA folding and RNA in embryos at single-cell resolution. Nature 568:49–54
    [Google Scholar]
  150. 150. 
    King HW, Fursova NA, Blackledge NP, Klose RJ 2018. Polycomb repressive complex 1 shapes the nucleosome landscape but not accessibility at target genes. Genome Res 28:1494–507
    [Google Scholar]
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