Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release

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Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release. / Narita, Takeo; Ito, Shinsuke; Higashijima, Yoshiki; Chu, Wai Kit; Neumann, Katrin; Walter, Jonas; Satpathy, Shankha; Liebner, Tim; Hamilton, William B; Maskey, Elina; Prus, Gabriela; Shibata, Marika; Iesmantavicius, Vytautas; Brickman, Joshua M; Anastassiadis, Konstantinos; Koseki, Haruhiko; Choudhary, Chunaram.

In: Molecular Cell, Vol. 81, No. 10, 2021, p. 2166-2182.e6.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Narita, T, Ito, S, Higashijima, Y, Chu, WK, Neumann, K, Walter, J, Satpathy, S, Liebner, T, Hamilton, WB, Maskey, E, Prus, G, Shibata, M, Iesmantavicius, V, Brickman, JM, Anastassiadis, K, Koseki, H & Choudhary, C 2021, 'Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release', Molecular Cell, vol. 81, no. 10, pp. 2166-2182.e6. https://doi.org/10.1016/j.molcel.2021.03.008

APA

Narita, T., Ito, S., Higashijima, Y., Chu, W. K., Neumann, K., Walter, J., Satpathy, S., Liebner, T., Hamilton, W. B., Maskey, E., Prus, G., Shibata, M., Iesmantavicius, V., Brickman, J. M., Anastassiadis, K., Koseki, H., & Choudhary, C. (2021). Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release. Molecular Cell, 81(10), 2166-2182.e6. https://doi.org/10.1016/j.molcel.2021.03.008

Vancouver

Narita T, Ito S, Higashijima Y, Chu WK, Neumann K, Walter J et al. Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release. Molecular Cell. 2021;81(10):2166-2182.e6. https://doi.org/10.1016/j.molcel.2021.03.008

Author

Narita, Takeo ; Ito, Shinsuke ; Higashijima, Yoshiki ; Chu, Wai Kit ; Neumann, Katrin ; Walter, Jonas ; Satpathy, Shankha ; Liebner, Tim ; Hamilton, William B ; Maskey, Elina ; Prus, Gabriela ; Shibata, Marika ; Iesmantavicius, Vytautas ; Brickman, Joshua M ; Anastassiadis, Konstantinos ; Koseki, Haruhiko ; Choudhary, Chunaram. / Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release. In: Molecular Cell. 2021 ; Vol. 81, No. 10. pp. 2166-2182.e6.

Bibtex

@article{2f7d3c4e53094cfda1166a04dda80e0b,
title = "Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release",
abstract = "The metazoan-specific acetyltransferase p300/CBP is involved in activating signal-induced, enhancer-mediated transcription of cell-type-specific genes. However, the global kinetics and mechanisms of p300/CBP activity-dependent transcription activation remain poorly understood. We performed genome-wide, time-resolved analyses to show that enhancers and super-enhancers are dynamically activated through p300/CBP-catalyzed acetylation, deactivated by the opposing deacetylase activity, and kinetic acetylation directly contributes to maintaining cell identity at very rapid (minutes) timescales. The acetyltransferase activity is dispensable for the recruitment of p300/CBP and transcription factors but essential for promoting the recruitment of TFIID and RNAPII at virtually all enhancers and enhancer-regulated genes. This identifies pre-initiation complex assembly as a dynamically controlled step in the transcription cycle and reveals p300/CBP-catalyzed acetylation as the signal that specifically promotes transcription initiation at enhancer-regulated genes. We propose that p300/CBP activity uses a {"}recruit-and-release{"} mechanism to simultaneously promote RNAPII recruitment and pause release and thereby enables kinetic activation of enhancer-mediated transcription.",
author = "Takeo Narita and Shinsuke Ito and Yoshiki Higashijima and Chu, {Wai Kit} and Katrin Neumann and Jonas Walter and Shankha Satpathy and Tim Liebner and Hamilton, {William B} and Elina Maskey and Gabriela Prus and Marika Shibata and Vytautas Iesmantavicius and Brickman, {Joshua M} and Konstantinos Anastassiadis and Haruhiko Koseki and Chunaram Choudhary",
year = "2021",
doi = "10.1016/j.molcel.2021.03.008",
language = "English",
volume = "81",
pages = "2166--2182.e6",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "10",

}

RIS

TY - JOUR

T1 - Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release

AU - Narita, Takeo

AU - Ito, Shinsuke

AU - Higashijima, Yoshiki

AU - Chu, Wai Kit

AU - Neumann, Katrin

AU - Walter, Jonas

AU - Satpathy, Shankha

AU - Liebner, Tim

AU - Hamilton, William B

AU - Maskey, Elina

AU - Prus, Gabriela

AU - Shibata, Marika

AU - Iesmantavicius, Vytautas

AU - Brickman, Joshua M

AU - Anastassiadis, Konstantinos

AU - Koseki, Haruhiko

AU - Choudhary, Chunaram

PY - 2021

Y1 - 2021

N2 - The metazoan-specific acetyltransferase p300/CBP is involved in activating signal-induced, enhancer-mediated transcription of cell-type-specific genes. However, the global kinetics and mechanisms of p300/CBP activity-dependent transcription activation remain poorly understood. We performed genome-wide, time-resolved analyses to show that enhancers and super-enhancers are dynamically activated through p300/CBP-catalyzed acetylation, deactivated by the opposing deacetylase activity, and kinetic acetylation directly contributes to maintaining cell identity at very rapid (minutes) timescales. The acetyltransferase activity is dispensable for the recruitment of p300/CBP and transcription factors but essential for promoting the recruitment of TFIID and RNAPII at virtually all enhancers and enhancer-regulated genes. This identifies pre-initiation complex assembly as a dynamically controlled step in the transcription cycle and reveals p300/CBP-catalyzed acetylation as the signal that specifically promotes transcription initiation at enhancer-regulated genes. We propose that p300/CBP activity uses a "recruit-and-release" mechanism to simultaneously promote RNAPII recruitment and pause release and thereby enables kinetic activation of enhancer-mediated transcription.

AB - The metazoan-specific acetyltransferase p300/CBP is involved in activating signal-induced, enhancer-mediated transcription of cell-type-specific genes. However, the global kinetics and mechanisms of p300/CBP activity-dependent transcription activation remain poorly understood. We performed genome-wide, time-resolved analyses to show that enhancers and super-enhancers are dynamically activated through p300/CBP-catalyzed acetylation, deactivated by the opposing deacetylase activity, and kinetic acetylation directly contributes to maintaining cell identity at very rapid (minutes) timescales. The acetyltransferase activity is dispensable for the recruitment of p300/CBP and transcription factors but essential for promoting the recruitment of TFIID and RNAPII at virtually all enhancers and enhancer-regulated genes. This identifies pre-initiation complex assembly as a dynamically controlled step in the transcription cycle and reveals p300/CBP-catalyzed acetylation as the signal that specifically promotes transcription initiation at enhancer-regulated genes. We propose that p300/CBP activity uses a "recruit-and-release" mechanism to simultaneously promote RNAPII recruitment and pause release and thereby enables kinetic activation of enhancer-mediated transcription.

U2 - 10.1016/j.molcel.2021.03.008

DO - 10.1016/j.molcel.2021.03.008

M3 - Journal article

C2 - 33765415

VL - 81

SP - 2166-2182.e6

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 10

ER -

ID: 259629030