Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Nature Pub. Group
    • Subject Terms:
      Epigenesis, Genetic* ; Gene Silencing* ; Protein Processing, Post-Translational*; Chromatin/*metabolism ; Polycomb Repressive Complex 1/*genetics ; Polycomb Repressive Complex 2/*genetics; Animals ; Cell Line ; Chromatin/chemistry ; Feedback, Physiological ; Histones/genetics ; Histones/metabolism ; Inheritance Patterns ; Mice ; Mitosis ; Mouse Embryonic Stem Cells/cytology ; Mouse Embryonic Stem Cells/metabolism ; Polycomb Repressive Complex 1/metabolism ; Polycomb Repressive Complex 2/metabolism ; Transcription, Genetic
    • Abstract:
      Polycomb group (PcG) proteins play critical roles in the epigenetic inheritance of cell fate. The Polycomb Repressive Complexes PRC1 and PRC2 catalyse distinct chromatin modifications to enforce gene silencing, but how transcriptional repression is propagated through mitotic cell divisions remains a key unresolved question. Using reversible tethering of PcG proteins to ectopic sites in mouse embryonic stem cells, here we show that PRC1 can trigger transcriptional repression and Polycomb-dependent chromatin modifications. We find that canonical PRC1 (cPRC1), but not variant PRC1, maintains gene silencing through cell division upon reversal of tethering. Propagation of gene repression is sustained by cis-acting histone modifications, PRC2-mediated H3K27me3 and cPRC1-mediated H2AK119ub1, promoting a sequence-independent feedback mechanism for PcG protein recruitment. Thus, the distinct PRC1 complexes present in vertebrates can differentially regulate epigenetic maintenance of gene silencing, potentially enabling dynamic heritable responses to complex stimuli. Our findings reveal how PcG repression is potentially inherited in vertebrates.
    • References:
      Science. 2017 Apr 7;356(6333):. (PMID: 28302795)
      Science. 2015 Apr 3;348(6230):132-5. (PMID: 25838386)
      Cell Rep. 2014 Jun 12;7(5):1456-1470. (PMID: 24857660)
      Dev Cell. 2004 Nov;7(5):663-76. (PMID: 15525528)
      Annu Rev Genet. 2004;38:413-43. (PMID: 15568982)
      Mol Cell. 2013 Mar 7;49(5):808-24. (PMID: 23473600)
      Nat Commun. 2016 Nov 28;7:13661. (PMID: 27892467)
      Nature. 2017 Oct 5;550(7674):114-118. (PMID: 28953874)
      Science. 2004 Nov 26;306(5701):1574-7. (PMID: 15567868)
      Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):E3415-21. (PMID: 25092339)
      Nature. 2009 Oct 8;461(7265):762-7. (PMID: 19767730)
      Nature. 2017 Sep 14;549(7671):287-291. (PMID: 28869966)
      Science. 2013 Feb 8;339(6120):698-9. (PMID: 23393264)
      Mol Cell Biol. 2006 Apr;26(7):2560-9. (PMID: 16537902)
      Mol Cell. 2012 Feb 10;45(3):344-56. (PMID: 22325352)
      Science. 2002 Nov 1;298(5595):1039-43. (PMID: 12351676)
      Nat Struct Mol Biol. 2017 Dec;24(12):1039-1047. (PMID: 29058710)
      Nature. 2012 Dec 6;492(7427):108-12. (PMID: 23051747)
      PLoS Genet. 2010 Dec 09;6(12):e1001244. (PMID: 21170310)
      EMBO J. 2006 Jul 12;25(13):3110-22. (PMID: 16763550)
      EMBO J. 1995 Mar 15;14(6):1209-20. (PMID: 7720711)
      Cell. 2002 Oct 18;111(2):197-208. (PMID: 12408864)
      Science. 2017 Apr 7;356(6333):85-88. (PMID: 28302792)
      Cell. 2014 Jun 5;157(6):1445-1459. (PMID: 24856970)
      Nat Rev Mol Cell Biol. 2015 Nov;16(11):643-649. (PMID: 26420232)
      Mol Cell. 2010 May 14;38(3):452-64. (PMID: 20471950)
      Elife. 2016 Oct 05;5:. (PMID: 27705745)
      Nat Struct Mol Biol. 2018 Mar;25(3):225-232. (PMID: 29483650)
      Nat Commun. 2015 Jun 22;6:7307. (PMID: 26095772)
      Cell Rep. 2013 Jan 31;3(1):60-9. (PMID: 23273917)
      Nat Struct Mol Biol. 2013 Oct;20(10):1147-55. (PMID: 24096405)
      Cell. 2012 Feb 17;148(4):664-78. (PMID: 22325148)
      Nat Chem Biol. 2016 Mar;12(3):180-7. (PMID: 26807715)
      Science. 2015 Apr 3;348(6230):1258699. (PMID: 25831549)
      Nat Methods. 2009 Dec;6(12):917-22. (PMID: 19915560)
      Nat Genet. 2011 Oct 02;43(11):1091-7. (PMID: 21964573)
      Elife. 2012 Dec 18;1:e00205. (PMID: 23256043)
      Science. 2014 Sep 19;345(6203):1515-8. (PMID: 25237104)
      Nat Genet. 2018 Jul;50(7):1002-1010. (PMID: 29808031)
      Nat Cell Biol. 2008 Nov;10(11):1291-300. (PMID: 18931660)
      Cell. 2012 Jun 22;149(7):1447-60. (PMID: 22704655)
      Curr Biol. 2016 Jul 25;26(14):R644-8. (PMID: 27458904)
      Nat Struct Mol Biol. 2014 Jun;21(6):569-71. (PMID: 24837194)
      Mol Cell Biol. 2007 May;27(10):3769-79. (PMID: 17339329)
    • Grant Information:
      R01 CA218392 United States CA NCI NIH HHS; R01 GM100919 United States GM NIGMS NIH HHS
    • Accession Number:
      0 (Chromatin)
      0 (Histones)
      EC 2.1.1.43 (Polycomb Repressive Complex 2)
      EC 2.3.2.27 (Polycomb Repressive Complex 1)
    • Publication Date:
      Date Created: 20190501 Date Completed: 20190508 Latest Revision: 20240716
    • Publication Date:
      20240716
    • Accession Number:
      PMC6488670
    • Accession Number:
      10.1038/s41467-019-09628-6
    • Accession Number:
      31036804