BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.
Animals
B-Lymphocytes
/ cytology
CRISPR-Cas Systems
Cell Cycle Proteins
/ genetics
Cell Line, Tumor
Drosophila melanogaster
Gene Editing
Haploidy
HeLa Cells
Histones
/ genetics
Humans
Polycomb Repressive Complex 1
/ genetics
Protein Processing, Post-Translational
Repressor Proteins
/ genetics
Sf9 Cells
Spodoptera
Transcription Factors
/ genetics
Transcriptional Activation
Tumor Suppressor Proteins
/ genetics
Ubiquitin Thiolesterase
/ genetics
Ubiquitination
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 01 2019
21 01 2019
Historique:
received:
02
01
2018
accepted:
21
12
2018
entrez:
22
1
2019
pubmed:
22
1
2019
medline:
6
2
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30664650
doi: 10.1038/s41467-018-08255-x
pii: 10.1038/s41467-018-08255-x
pmc: PMC6341105
doi:
Substances chimiques
ASXL1 protein, human
0
ASXL2 protein, human
0
ASXL3 protein, human
0
BAP1 protein, human
0
Cell Cycle Proteins
0
Histones
0
PRC1 protein, human
0
Repressor Proteins
0
Transcription Factors
0
Tumor Suppressor Proteins
0
Polycomb Repressive Complex 1
EC 2.3.2.27
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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