PR-DUB maintains the expression of critical genes through FOXK1/2- A nd ASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1 deubiquitination Journal Article
| Authors: | Kolovos, P.; Nishimura, K.; Sankar, A.; Sidoli, S.; Cloos, P. A.; Helin, K.; Christensen, J. |
| Article Title: | PR-DUB maintains the expression of critical genes through FOXK1/2- A nd ASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1 deubiquitination |
| Abstract: | 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. © 2020 Kolovos et al. |
| Journal Title: | Genome Research |
| Volume: | 30 |
| Issue: | 8 |
| ISSN: | 1088-9051 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2020-08-01 |
| Start Page: | 1119 |
| End Page: | 1130 |
| Language: | English |
| DOI: | 10.1101/gr.261016.120 |
| PUBMED: | 32747411 |
| PROVIDER: | scopus |
| PMCID: | PMC7462075 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2020 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work