TY - JOUR
T1 - PR-DUB maintains the expression of critical genes through FOXK1/2- A nd ASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1 deubiquitination
AU - Kolovos, Petros
AU - Nishimura, Koutarou
AU - Sankar, Aditya
AU - Sidoli, Simone
AU - Cloos, Paul A.
AU - Helin, Kristian
AU - Christensen, Jesper
N1 - Publisher Copyright:
© 2020 Kolovos et al.
PY - 2020/8/3
Y1 - 2020/8/3
N2 - 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.
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.
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U2 - 10.1101/gr.261016.120
DO - 10.1101/gr.261016.120
M3 - Article
C2 - 32747411
AN - SCOPUS:85090079585
SN - 1088-9051
VL - 30
SP - 1119
EP - 1130
JO - Genome research
JF - Genome research
IS - 8
ER -