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

Novo Nordisk Foundation
Center for Protein Research

Research output: Contribution to journal › Journal article › Research › peer-review

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

In: Cell, Vol. 174, No. 1, 2018, p. 231-244.e12.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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 2018, 'Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome', Cell, vol. 174, no. 1, pp. 231-244.e12. https://doi.org/10.1016/j.cell.2018.04.033

APA

Weinert, B. T., Narita, T., Satpathy, S., Srinivasan, B., Hansen, B. K., Schölz, C., Hamilton, W. B., Zucconi, B. E., Wang, W. W., Liu, W. R., Brickman, J. M., Kesicki, E. A., Lai, A., Bromberg, K. D., Cole, P. A., & Choudhary, C. (2018). Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome. Cell, 174(1), 231-244.e12. https://doi.org/10.1016/j.cell.2018.04.033

Vancouver

Weinert BT, Narita T, Satpathy S, Srinivasan B, Hansen BK, Schölz C et al. Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome. Cell. 2018;174(1):231-244.e12. https://doi.org/10.1016/j.cell.2018.04.033

Author

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. / Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome. In: Cell. 2018 ; Vol. 174, No. 1. pp. 231-244.e12.

Bibtex

@article{3b57fdcb2f8d4873a650ad358f3c7faa,

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

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 (<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.",

keywords = "A-485, acetylation, acetylation kinetics, bromodomain, CBP, enhancer, gene transcription, mass spectrometry, p300, proteomics",

author = "Weinert, {Brian T.} and Takeo Narita and Shankha Satpathy and Balaji Srinivasan and Hansen, {Bogi K} and Christian Sch{\"o}lz and Hamilton, {William B.} and Zucconi, {Beth E} and Wang, {Wesley W} and Liu, {Wenshe R} and Brickman, {Joshua M} and Kesicki, {Edward A} and Albert Lai and Bromberg, {Kenneth D} and Cole, {Philip A} and Chunaram Choudhary",

year = "2018",

doi = "10.1016/j.cell.2018.04.033",

language = "English",

volume = "174",

pages = "231--244.e12",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "1",

}

RIS

TY - JOUR

T1 - Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome

AU - Weinert, Brian T.

AU - Narita, Takeo

AU - Satpathy, Shankha

AU - Srinivasan, Balaji

AU - Hansen, Bogi K

AU - Schölz, Christian

AU - Hamilton, William B.

AU - Zucconi, Beth E

AU - Wang, Wesley W

AU - Liu, Wenshe R

AU - Brickman, Joshua M

AU - Kesicki, Edward A

AU - Lai, Albert

AU - Bromberg, Kenneth D

AU - Cole, Philip A

AU - Choudhary, Chunaram

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - A-485

KW - acetylation

KW - acetylation kinetics

KW - bromodomain

KW - CBP

KW - enhancer

KW - gene transcription

KW - mass spectrometry

KW - p300

KW - proteomics

U2 - 10.1016/j.cell.2018.04.033

DO - 10.1016/j.cell.2018.04.033

M3 - Journal article

C2 - 29804834

VL - 174

SP - 231-244.e12

JO - Cell

JF - Cell

SN - 0092-8674

IS - 1

ER -

ID: 197765182

Novo Nordisk Foundation Center for Protein Research