Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome

Research output: Contribution to journalJournal articleResearchpeer-review

Brian T. Weinert, Takeo Narita, Shankha Satpathy, Balaji Srinivasan, Bogi K Hansen, Christian Schölz, William B. Hamilton, Beth E Zucconi, Wesley W Wang, Wenshe R Liu, Joshua M Brickman, Edward A Kesicki, Albert Lai, Kenneth D Bromberg, Philip A Cole, Chunaram Choudhary

The acetyltransferases CBP and p300 are multifunctional transcriptional co-activators. Here, we combined quantitative proteomics with CBP/p300-specific catalytic inhibitors, bromodomain inhibitor, and gene knockout to reveal a comprehensive map of regulated acetylation sites and their dynamic turnover rates. CBP/p300 acetylates thousands of sites, including signature histone sites and a multitude of sites on signaling effectors and enhancer-associated transcriptional regulators. Time-resolved acetylome analyses identified a subset of CBP/p300-regulated sites with very rapid (<30 min) acetylation turnover, revealing a dynamic balance between acetylation and deacetylation. Quantification of acetylation, mRNA, and protein abundance after CBP/p300 inhibition reveals a kinetically competent network of gene expression that strictly depends on CBP/p300-catalyzed rapid acetylation. Collectively, our in-depth acetylome analyses reveal systems attributes of CBP/p300 targets, and the resource dataset provides a framework for investigating CBP/p300 functions and for understanding the impact of small-molecule inhibitors targeting its catalytic and bromodomain activities.

Original languageEnglish
JournalCell
Volume174
Issue number1
Pages (from-to)231-244.e12
Number of pages27
ISSN0092-8674
DOIs
Publication statusPublished - 2018

    Research areas

  • A-485, acetylation, acetylation kinetics, bromodomain, CBP, enhancer, gene transcription, mass spectrometry, p300, proteomics

ID: 197765182