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

Molecular cell | 2017

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.

Pubmed ID: 29056321 RIS Download

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA074305
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM025232
  • Agency: NIGMS NIH HHS, United States
    Id: R37 GM025232
  • Agency: NIGMS NIH HHS, United States
    Id: R37 GM062437

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