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/CBP in regulating promoter-proximal paused Pol II. We find that Drosophila CBP (nejire) inhibition impedes transcription through the +1 nucleosome leading to accumulation of Pol II at this position on all expressed genes. Promoters strongly occupied by CBP and GAGA-factor have high levels of paused Pol II, a unique chromatin signature and strong expression 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. This SuperSeries is composed of the SubSeries listed below. Drosophila melanogaster S2 cells were treated with control (C37) or the CBP inhibitor C646 for 10 min, fixed with with formaldehyde, and either digested with MNase or used in ChIP-seq with a TFIIB antibody. One percent Saccharomyces cerevisiae chromatin was mixed with MNase-digested chromatin, and one percent Drosophila virilis chromatin mixed with the chromatin used for ChIP-seq (spike-in).