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BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE110143 | GEO | 2018/11/21

REPOSITORIES: GEO

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BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.

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BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation

Project description: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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BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation

Project description:BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation

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