RT Journal
A1 Kolovos, Petros
A1 Nishimura, Koutarou
A1 Sankar, Aditya
A1 Sidoli, Simone
A1 Cloos, Paul A.
A1 Helin, Kristian
A1 Christensen, Jesper
T1 PR-DUB maintains the expression of critical genes through FOXK1/2- and ASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1 deubiquitination
JF Genome Research 
JO Genome Research 
YR 2020 
FD August 01 
VO 30 
IS 8 
SP 1119 
OP 1130 
DO 10.1101/gr.261016.120 
UL http://genome.cshlp.org/content/30/8/1119.abstract 
AB 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.