biostudies-literatureWeinert BTFAMRINovo Nordisk FoundationNovo NordiskNovo Nordisk Foundation Center for Protein ResearchDanish National Research Foundation (DNRF)Novo Nordisk Foundation Section for Basic Stem Cell BiologyNIHNovo Nordisk FondenNIGMS NIH HHS231-244.e12https://www.ebi.ac.uk/biostudies/studies/S-EPMC6078418biostudies-literatureUnknown174(1)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 netCellTime-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome.PMC6078418K99 GM124357R37 GM062437NNF14CC0001GM62437116PI Chunaram ChoudharyNNF15OC0017774Brickman group NNFNNF14OC0008541Choudhary CCole PASrinivasan BHamilton WBLai AZucconi BEWeinert BTLiu WRNarita TKesicki EASatpathy SScholz CBromberg KDWang WWBrickman JMHansen BKfalseTime-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome.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 net2018-01-01T00:00:00Z2018 Jun2026-05-04T13:27:17.963Z2019-07-25T07:07:58ZS-EPMC60784182980483410.1016/j.cell.2018.04.033