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Polycomb group proteins (PcG) are transcriptional repressors that control cell identity and development. In mammals, five different CBX proteins associate with the core Polycomb repressive complex 1 (PRC1). In mouse embryonic stem cells (ESCs), CBX6 and CBX7 are the most highly expressed CBX family members. CBX7 has been recently characterized, but little is known regarding the function of CBX6. Here, we show that CBX6 is essential for ESC identity. Its depletion destabilizes the pluripotency network and triggers differentiation. Mechanistically, we find that CBX6 is physically and functionally associated to both canonical PRC1 (cPRC1) and non-canonical PRC1 (ncPRC1) complexes. Notably, in contrast to CBX7, CBX6 is recruited to chromatin independently of H3K27me3. Taken together, our findings reveal that CBX6 is an essential component of ESC biology that contributes to the structural and functional complexity of the PRC1 complex.

Titel:	The Polycomb group protein CBX6 is an essential regulator of embryonic stem cell identity.
Autor/in / Beteiligte Person:	Santanach, A ; Blanco, E ; Jiang, H ; Molloy, KR ; Sansó, M ; LaCava, J ; Morey, L ; Di Croce, L
Zeitschrift:	Nature communications, Jg. 8 (2017-11-01), Heft 1, S. 1235
Veröffentlichung:	[London] : Nature Pub. Group, 2017
Medientyp:	academicJournal
ISSN:	2041-1723 (electronic)
DOI:	10.1038/s41467-017-01464-w
Schlagwort:	Animals HEK293 Cells Humans Mice Mouse Embryonic Stem Cells cytology Polycomb Repressive Complex 1 genetics Polycomb Repressive Complex 1 metabolism Polycomb-Group Proteins metabolism RNA Interference Cell Differentiation genetics Gene Expression Profiling Mouse Embryonic Stem Cells metabolism Polycomb-Group Proteins genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Nat Commun] 2017 Nov 01; Vol. 8 (1), pp. 1235. <i>Date of Electronic Publication: </i>2017 Nov 01. MeSH Terms: Gene Expression Profiling* ; Cell Differentiation / genetics ; Mouse Embryonic Stem Cells / metabolism ; Polycomb-Group Proteins / *genetics ; Animals ; HEK293 Cells ; Humans ; Mice ; Mouse Embryonic Stem Cells / cytology ; Polycomb Repressive Complex 1 / genetics ; Polycomb Repressive Complex 1 / metabolism ; Polycomb-Group Proteins / metabolism ; RNA Interference References: Development. 2008 Apr;135(8):1513-24. (PMID: 18339675) ; Dev Cell. 2004 Nov;7(5):663-76. (PMID: 15525528) ; Cell Stem Cell. 2012 Jan 6;10(1):47-62. (PMID: 22226355) ; J Vis Exp. 2016 Dec 9;(118):. (PMID: 28060343) ; J Cell Biol. 2007 Jul 16;178(2):219-29. (PMID: 17620408) ; Bioinformatics. 2009 May 1;25(9):1105-11. (PMID: 19289445) ; Sci Adv. 2015 Dec 04;1(11):e1500737. (PMID: 26665172) ; Cell. 2012 Feb 17;148(4):664-78. (PMID: 22325148) ; Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7. (PMID: 27141961) ; Cell Stem Cell. 2014 Jun 5;14(6):735-51. (PMID: 24905164) ; Nat Protoc. 2013 Nov;8(11):2281-2308. (PMID: 24157548) ; Nat Struct Mol Biol. 2016 Jul;23(7):682-690. (PMID: 27294783) ; Mol Cell. 2011 May 20;42(4):438-50. (PMID: 21596310) ; Genome Biol. 2009;10(3):R25. (PMID: 19261174) ; Nat Biotechnol. 2010 May;28(5):511-5. (PMID: 20436464) ; Nature. 1978 Dec 7;276(5688):565-70. (PMID: 103000) ; Mol Cell. 2012 Feb 10;45(3):344-56. (PMID: 22325352) ; Cell Stem Cell. 2012 Sep 7;11(3):319-32. (PMID: 22770845) ; BMC Genomics. 2009 Nov 20;10:549. (PMID: 19930571) ; Nat Rev Mol Cell Biol. 2009 Oct;10(10):697-708. (PMID: 19738629) ; Biotechniques. 2012 May;0(0):1-6. (PMID: 22668517) ; Trends Genet. 2007 Oct;23(10):494-502. (PMID: 17825942) ; ACS Med Chem Lett. 2015 Dec 07;7(2):139-44. (PMID: 26985288) ; Genome Biol. 2014 Feb 03;15(2):R23. (PMID: 24485159) ; Curr Opin Genet Dev. 2004 Apr;14(2):155-64. (PMID: 15196462) ; Mol Cell Proteomics. 2011 Apr;10(4):M110.002642. (PMID: 21282530) ; Nat Struct Mol Biol. 2013 Oct;20(10):1147-55. (PMID: 24096405) ; PLoS Genet. 2012;8(7):e1002774. (PMID: 22844243) ; J Med Chem. 2014 Apr 10;57(7):2874-83. (PMID: 24625057) ; Cell Stem Cell. 2012 Jan 6;10(1):33-46. (PMID: 22226354) ; Elife. 2012 Dec 18;1:e00205. (PMID: 23256043) ; Mol Cell Proteomics. 2014 Sep;13(9):2513-26. (PMID: 24942700) ; Mol Cell Biol. 2006 Apr;26(7):2560-9. (PMID: 16537902) ; Cell Stem Cell. 2015 Sep 3;17(3):300-15. (PMID: 26340528) ; Elife. 2017 Mar 17;6:. (PMID: 28304275) Grant Information: P41 GM103314 United States GM NIGMS NIH HHS; P41 GM109824 United States GM NIGMS NIH HHS Substance Nomenclature: 0 (Cbx6 protein, mouse) ; 0 (Polycomb-Group Proteins) ; EC 2.3.2.27 (Polycomb Repressive Complex 1) Entry Date(s): Date Created: 20171102 Date Completed: 20180905 Latest Revision: 20240604 Update Code: 20240604 PubMed Central ID: PMC5663739

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The Polycomb group protein CBX6 is an essential regulator of embryonic stem cell identity.