PR-DUB maintains expression of critical genes through FOXK1/2 and ASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1 deubiquitination
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PR-DUB maintains expression of critical genes through FOXK1/2 and ASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1 deubiquitination. / Kolovos, Petros; Nishimura, Koutarou; Sankar, Aditya; Sidoli, Simone; Cloos, Paul A; Helin, Kristian; Christensen, Jesper.
In: Genome Research, Vol. 30, No. 8, 08.2020, p. 1119-1130.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - PR-DUB maintains expression of critical genes through FOXK1/2 and 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 - Published by Cold Spring Harbor Laboratory Press.
PY - 2020/8
Y1 - 2020/8
N2 - Polycomb group proteins are important for maintaining gene expression patterns and cell identity in metazoans. The mammalian Polycomb repressive de-ubiquitinase (PR-DUB) complexes catalyze removal of monoubiquitination on lysine 119 of histone H2A (H2AK119Ub1) through a multi-protein 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 previously was 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 de-ubiquitinase (PR-DUB) complexes catalyze removal of monoubiquitination on lysine 119 of histone H2A (H2AK119Ub1) through a multi-protein 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 previously was 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.
U2 - 10.1101/gr.261016.120
DO - 10.1101/gr.261016.120
M3 - Journal article
C2 - 32747411
VL - 30
SP - 1119
EP - 1130
JO - Genome Research
JF - Genome Research
SN - 1088-9051
IS - 8
ER -
ID: 245895110