Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome. Academic Article uri icon

abstract

  • 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 (<30min) 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.

published proceedings

  • Cell

altmetric score

  • 65.1

author list (cited authors)

  • Weinert, B. T., Narita, T., Satpathy, S., Srinivasan, B., Hansen, B. K., Schlz, C., ... Choudhary, C.

citation count

  • 222

complete list of authors

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

publication date

  • June 2018

published in