Maintenance of appropriate cell states involves epigenetic mechanisms, including Polycomb-group (PcG)-mediated transcriptional repression. While PcG proteins are known to induce chromatin compaction, how PcG proteins gain access to DNA in compact chromatin to achieve long-term silencing is poorly understood. Here, we show that the p300/CREB-binding protein (CBP) co-activator is associated with two-thirds of PcG regions and required for PcG occupancy at many of these in Drosophila and mouse cells. CBP stabilizes RNA polymerase II (Pol II) at PcG-bound repressive sites and promotes Pol II pausing independently of its histone acetyltransferase activity. CBP and Pol II pausing are necessary for RNA-DNA hybrid (R-loop) formation and nucleosome depletion at Polycomb Response Elements (PREs), whereas transcription beyond the pause region is not. These results suggest that non-enzymatic activities of the CBP co-activator have been repurposed to support PcG-mediated silencing, revealing how chromatin regulator interplay maintains transcriptional states.

维持适当的细胞状态涉及表观遗传机制，包括 Polycomb 组 (PcG) 介导的转录抑制。虽然已知 PcG 蛋白会诱导染色质压实，但人们对 PcG 蛋白如何进入致密染色质中的 DNA 以实现长期沉默知之甚少。在这里，我们表明 p300/CREB ​​结合蛋白 (CBP) 共激活因子与三分之二的 PcG 区域相关，并且是果蝇中许多 PcG 占据所必需的和小鼠细胞。CBP 在 PcG 结合的抑制位点稳定 RNA 聚合酶 II (Pol II)，并独立于其组蛋白乙酰转移酶活性促进 Pol II 暂停。CBP 和 Pol II 暂停对于 RNA-DNA 杂交（R 环）形成和 Polycomb 反应元件（PRE）的核小体耗竭是必需的，而暂停区域以外的转录则不是。这些结果表明， CBP共激活剂的非酶活性已被重新用于支持 PcG 介导的沉默，揭示了染色质调节因子相互作用如何维持转录状态。