BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation

• DOI: 10.1038/s41467-018-08255-x
• Publication Date: 2019-01-21T11:02:40Z
• Authors: Antoine Campagne; Ming-Kang Lee; Dina Zielinski; Audrey Michaud; Stéphanie Le Corre; Florent Dingli; Hong Chen; Lara Z. Shahidian; Ivaylo Vassilev; Nicolas Servant; Damarys Loew; Eric Pasmant; Sophie Postel-Vinay; Michel Wassef; Raphaël Margueron
• Keywords: Deubiquitinating enzyme; Transcription

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