PR-DUB maintains the expression of critical genes through FOXK1/2- and ASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1 deubiquitination.
Animals
Cell Proliferation
/ genetics
Cells, Cultured
Chromatin
/ genetics
Deubiquitinating Enzymes
/ genetics
Forkhead Transcription Factors
/ metabolism
Gene Expression Regulation
/ genetics
Gene Knockout Techniques
Histones
/ metabolism
Mice
Mice, Inbred BALB C
Mice, Knockout
Mouse Embryonic Stem Cells
Polycomb-Group Proteins
/ genetics
Repressor Proteins
/ metabolism
Tumor Suppressor Proteins
/ metabolism
Ubiquitin Thiolesterase
/ metabolism
Journal
Genome research
ISSN: 1549-5469
Titre abrégé: Genome Res
Pays: United States
ID NLM: 9518021
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
10
01
2020
accepted:
10
07
2020
pubmed:
5
8
2020
medline:
11
11
2021
entrez:
5
8
2020
Statut:
ppublish
Résumé
Polycomb group proteins are important for maintaining gene expression patterns and cell identity in metazoans. The mammalian Polycomb repressive deubiquitinase (PR-DUB) complexes catalyze removal of monoubiquitination on lysine 119 of histone H2A (H2AK119ub1) through a multiprotein core comprised of BAP1, HCFC1, FOXK1/2, and OGT in combination with either of ASXL1, 2, or 3. Mutations in PR-DUB components are frequent in cancer. However, mechanistic understanding of PR-DUB function in gene regulation is limited. Here, we show that BAP1 is dependent on the ASXL proteins and FOXK1/2 in facilitating gene activation across the genome. Although PR-DUB was previously shown to cooperate with PRC2, we observed minimal overlap and functional interaction between BAP1 and PRC2 in embryonic stem cells. Collectively, these results demonstrate that PR-DUB, by counteracting accumulation of H2AK119ub1, maintains chromatin in an optimal configuration ensuring expression of genes important for general functions such as cell metabolism and homeostasis.
Identifiants
pubmed: 32747411
pii: gr.261016.120
doi: 10.1101/gr.261016.120
pmc: PMC7462075
doi:
Substances chimiques
ASXL2 protein, mouse
0
Asxl1 protein, mouse
0
BAP1 protein, mouse
0
Chromatin
0
Forkhead Transcription Factors
0
FoxK2 protein, mouse
0
Foxk1 protein, mouse
0
Histones
0
Polycomb-Group Proteins
0
Repressor Proteins
0
Tumor Suppressor Proteins
0
Deubiquitinating Enzymes
EC 3.4.19.12
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1119-1130Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2020 Kolovos et al.; Published by Cold Spring Harbor Laboratory Press.
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