BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30664650.
- Also identified by DOI 10.1038/s41467-018-08255-x and PMC identifier 6341105.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- B-Lymphocytes
- Cell Cycle Proteins
- Histones
- Protein Processing, Post-Translational
- Tumor Suppressor Proteins
- Ubiquitin Thiolesterase