期刊
GENOME RESEARCH
卷 30, 期 8, 页码 1119-1130出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.261016.120
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资金
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Rubicon fellowship) [019.162LW.011]
- Marie Curie Individual Fellowship [H2020-MSCA-IF-2017]
- Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers, Japan Society for the Promotion of Science [S2704]
- Danish Cancer Society [R167-A10877]
- Danish National Research Foundation [DNRF82]
- Independent Research Fund Denmark [6153-000005, 701600067]
- Neye Foundation, through a center grant from the Novo Nordisk Fonden (NNF) [NNF17CC0027852]
- Neye Foundation, through Memorial Sloan Kettering Cancer Center Support Grant (National Institutes of Health) [P30 CA008748]
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.
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