MassIVE MSV000095981

Imported Reanalysis Dataset Public PXD005252

Time-resolved analysis reveals rapid dynamics and broad scope of the CBP/p300 acetylome

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Description

The acetyltransferases CBP and p300 are multifunctional transcriptional co-activators; however, their acetylation targets, site-specific acetylation kinetics, and function in proteome regulation are incompletely understood. We combined quantitative proteomics with novel CBP/p300-specific catalytic inhibitors, bromodomain inhibitor, and gene knockout to show that CBP/p300 acetylates thousands of sites, including signature histone sites, as well as a multitude of sites on signaling effectors and enhancer-associated transcriptional regulators. Kinetic analysis 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, as well as for understanding the impact of small molecule inhibitors targeting its catalytic and bromodomain activities. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Cbp ; Acetyltransferase ; Acetylation ; P300

Contact

Principal Investigators:
(in alphabetical order) 		Chunaram Choudhary, Proteomics Program Blegdamsvej 3 2200 K�benhavn N Bygning 6 Building: 06-2-36, N/A
Submitting User: ccms

Publications

Weinert BT, Narita T, Satpathy S, Srinivasan B, Hansen BK, Schölz C, Hamilton WB, Zucconi BE, Wang WW, Liu WR, Brickman JM, Kesicki EA, Lai A, Bromberg KD, Cole PA, Choudhary C.
Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome.
Cell. 2018 Jun 28;174(1):231-244.e12. Epub 2018 May 24.

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