Transcription activation involves RNA polymerase II (Pol II) recruitment and release from the promoter into productive elongation, but how specific chromatin regulators control these steps is unclear. Here, we identify a novel activity of the histone acetyltransferase p300/CREB-binding protein (CBP) in regulating promoter-proximal paused Pol II. We find that Drosophila CBP inhibition results in “dribbling” of Pol II from the pause site to positions further downstream but impedes transcription through the +1 nucleosome genome-wide. Promoters strongly occupied by CBP and GAGA factor have high levels of paused Pol II, a unique chromatin signature, and are highly expressed regardless of cell type. Interestingly, CBP activity is rate limiting for Pol II recruitment to these highly paused promoters through an interaction with TFIIB but for transit into elongation by histone acetylation at other genes. Thus, CBP directly stimulates both Pol II recruitment and the ability to traverse the first nucleosome, thereby promoting transcription of most genes.

转录激活涉及 RNA 聚合酶 II (Pol II) 募集和从启动子释放进入生产性延伸，但具体染色质调节剂如何控制这些步骤尚不清楚。在这里，我们确定了组蛋白乙酰转移酶 p300/CREB ​​结合蛋白 (CBP) 在调节启动子近端暂停 Pol II 中的新活性。我们发现 果蝇CBP 抑制导致 Pol II 从暂停位点“运球”到更下游的位置，但阻碍了通过 +1 核小体全基因组的转录。被 CBP 和 GAGA 因子强烈占据的启动子具有高水平的暂停 Pol II，这是一种独特的染色质特征，并且无论细胞类型如何都高度表达。有趣的是，CBP 活动通过与 TFIIB 的相互作用限制 Pol II 招募到这些高度暂停的启动子，但通过其他基因的组蛋白乙酰化转变为延伸。因此，CBP 直接刺激 Pol II 募集和穿越第一个核小体的能力，从而促进大多数基因的转录。