CBP Regulates Recruitment and Release of Promoter-Proximal RNA Polymerase II

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. CBP and p300 have known functions at transcriptional enhancers. Boija et al. identify a regulatory role for the Drosophila p300/CBP homolog also at promoters. Drosophila CBP maintains RNA Pol II at the promoter-proximal pause site, recruits Pol II through an interaction with TFIIB, and facilitates transcription through the +1 nucleosome.