TY - JOUR
T1 - BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation
AU - Campagne, Antoine
AU - Lee, Ming Kang
AU - Zielinski, Dina
AU - Michaud, Audrey
AU - Le Corre, Stéphanie
AU - Dingli, Florent
AU - Chen, Hong
AU - Shahidian, Lara Z.
AU - Vassilev, Ivaylo
AU - Servant, Nicolas
AU - Loew, Damarys
AU - Pasmant, Eric
AU - Postel-Vinay, Sophie
AU - Wassef, Michel
AU - Margueron, Raphaël
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85060237126&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-08255-x
DO - 10.1038/s41467-018-08255-x
M3 - Article
C2 - 30664650
AN - SCOPUS:85060237126
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 348
ER -