PR-DUB maintains the expression of critical genes through FOXK1/2- A nd ASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1 deubiquitination

Petros Kolovos, Koutarou Nishimura, Aditya Sankar, Simone Sidoli, Paul A. Cloos, Kristian Helin, Jesper Christensen

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1119-1130
Number of pages12
JournalGenome research
Volume30
Issue number8
DOIs
StatePublished - Aug 3 2020

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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