BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation

被引：102

作者：

Campagne, Antoine ^{[1
,2
]}

Lee, Ming-Kang ^{[1
,2
]}

Zielinski, Dina ^{[1
,2
,3
]}

Michaud, Audrey ^{[1
,2
]}

Le Corre, Stephanie ^{[1
,2
]}

Dingli, Florent ^{[1
]}

Chen, Hong ^{[1
,2
]}

Shahidian, Lara Z. ^{[4
]}

Vassilev, Ivaylo ^{[1
,2
,3
]}

Servant, Nicolas ^{[1
,3
]}

Loew, Damarys ^{[1
]}

Pasmant, Eric ^{[5
]}

Postel-Vinay, Sophie ^{[6
]}

Wassef, Michel ^{[1
,2
]}

Margueron, Raphael ^{[1
,2
]}

机构：

[1] Sorbonne Univ, Paris Sci & Lettres Res Univ, Inst Curie, F-75005 Paris, France

[2] CNRS, INSERM, U934, UMR3215, F-75005 Paris, France

[3] INSERM, Mines Paris Tech, U900, F-75005 Paris, France

[4] Helmholtz Zentrum Munchen, Inst Funct Epigenet, D-85764 Neuherberg, Germany

[5] Univ Paris 05, Cochin Hosp, AP HP, HUPC,Dept Mol Genet Pathol,Fac Pharm,EA7331, F-75014 Paris, France

[6] Univ Paris Saclay, INSERM, Dept Innovat Therapeut & Essais Precoces, Gustave Roussy,U981, F-94805 Villejuif, France

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

BRCA1-ASSOCIATED PROTEIN-1; UBIQUITIN HYDROLASE; ASXL1; MUTATIONS; POLYCOMB; CELLS; PRC2; METHYLATION; RECRUITMENT; REGULATOR; VERSATILE;

D O I：

10.1038/s41467-018-08255-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In Drosophila, a complex consisting of Calypso and ASX catalyzes H2A deubiquitination and has been reported to act as part of the Polycomb machinery in transcriptional silencing. The mammalian homologs of these proteins (BAP1 and ASXL1/2/3, respectively), are frequently mutated in various cancer types, yet their precise functions remain unclear. Using an integrative approach based on isogenic cell lines generated with CRISPR/Cas9, we uncover an unanticipated role for BAP1 in gene activation. This function requires the assembly of an enzymatically active BAP1-associated core complex (BAP1. com) containing one of the redundant ASXL proteins. We investigate the mechanism underlying BAP1. com-mediated transcriptional regulation and show that it does not participate in Polycomb-mediated silencing. Instead, our results establish that the function of BAP1. com is to safeguard transcriptionally active genes against silencing by the Polycomb Repressive Complex 1.

引用

页数：15

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