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BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.
Nat. Commun. 10:348 (2019)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Brca1-associated Protein-1; Ubiquitin Hydrolase; Asxl1 Mutations; Polycomb; Cells; Prc2; Methylation; Recruitment; Regulator; Versatile
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Journal
Nature Communications
Quellenangaben
Volume: 10,
Issue: 1,
Article Number: 348
Publisher
Nature Publishing Group
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Functional Epigenetics (IFE)