Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome.
Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome.
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DOI：
10.1016/j.cell.2018.04.033
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发表时间：
2018-06-28
期刊：
影响因子：
64.5
通讯作者：
Choudhary C
中科院分区：
文献类型：
--
作者：
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
乙酰基转移酶CBP和P300是多功能转录共激活因子。在这里，我们将定量蛋白质组学与CBP/p300特异性催化抑制剂、溴域抑制剂和基因敲除相结合，揭示了调控的乙酰化位点及其动态周转率的全面图谱。CBP/p300乙酰化数千个位点，包括标志性组蛋白位点，以及信号效应器和增强子相关转录调节因子上的大量位点。时间分辨乙酰组分析确定了CBP/p300调节位点的一个子集，具有非常快的乙酰化周转(<；30分钟)，揭示了乙酰化和去乙酰化之间的动态平衡。CBP/p300抑制后乙酰化、mRNA和蛋白质丰度的定量显示了一个严格依赖于CBP/p300催化的快速乙酰化的基因表达动力学网络。总而言之，我们深入的乙酰组分析揭示了CBP/p300靶标的系统属性，资源数据集为研究CBP/p300功能以及了解针对其催化和溴域活性的小分子抑制剂的影响提供了一个框架。
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, as well as 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, as well as for understanding the impact of small molecule inhibitors targeting its catalytic and bromodomain activities.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
64.8
作者：
Lasko LM;Jakob CG;Edalji RP;Qiu W;Montgomery D;Digiammarino EL;Hansen TM;Risi RM;Frey R;Manaves V;Shaw B;Algire M;Hessler P;Lam LT;Uziel T;Faivre E;Ferguson D;Buchanan FG;Martin RL;Torrent M;Chiang GG;Karukurichi K;Langston JW;Weinert BT;Choudhary C;de Vries P;Van Drie JH;McElligott D;Kesicki E;Marmorstein R;Sun C;Cole PA;Rosenberg SH;Michaelides MR;Lai A;Bromberg KD
通讯作者：
Bromberg KD
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
14.9
作者：
Chatr-Aryamontri A;Oughtred R;Boucher L;Rust J;Chang C;Kolas NK;O'Donnell L;Oster S;Theesfeld C;Sellam A;Stark C;Breitkreutz BJ;Dolinski K;Tyers M
通讯作者：
Tyers M
影响因子：
78.5
作者：
Murray, Iain A.;Patterson, Andrew D.;Perdew, Gary H.
通讯作者：
Perdew, Gary H.