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.

中文翻译：

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PR-DUB 通过 FOXK1/2 和 ASXL1/2/3 依赖性募集到染色质和 H2AK119ub1 去泛素化来维持关键基因的表达。

Polycomb 组蛋白对于维持后生动物的基因表达模式和细胞身份很重要。哺乳动物 Polycomb 抑制性去泛素化酶 (PR-DUB) 复合物通过由 BAP1、HCFC1、FOXK1/2 和 OGT 与 ASXL1、2 或3. PR-DUB 成分的突变在癌症中很常见。然而，对基因调控中 PR-DUB 功能的机制理解是有限的。在这里，我们表明 BAP1 依赖于 ASXL 蛋白和 FOXK1/2，以促进基因组中的基因激活。尽管先前已证明 PR-DUB 与 PRC2 合作，但我们在胚胎干细胞中观察到 BAP1 和 PRC2 之间的重叠和功能相互作用最小。总的来说，这些结果表明 PR-DUB、