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 -