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

Research output: Contribution to journalResearch articleContributedpeer-review


  • Takeo Narita - , University College Copenhagen (Author)
  • Shinsuke Ito - , RIKEN (Author)
  • Yoshiki Higashijima - , University College Copenhagen (Author)
  • Wai Kit Chu - , University College Copenhagen (Author)
  • Katrin Neumann - , Stem Cell Engineering Facility, Genetic Engineering of Stem Cells (Research Group) (Author)
  • Jonas Walter - , University College Copenhagen (Author)
  • Shankha Satpathy - , University College Copenhagen (Author)
  • Tim Liebner - , University College Copenhagen (Author)
  • William B Hamilton - , University College Copenhagen (Author)
  • Elina Maskey - , University College Copenhagen (Author)
  • Gabriela Prus - , University College Copenhagen (Author)
  • Marika Shibata - , RIKEN (Author)
  • Vytautas Iesmantavicius - , University College Copenhagen (Author)
  • Joshua M Brickman - , University College Copenhagen (Author)
  • Konstantinos Anastassiadis - , Genetic Engineering of Stem Cells (Research Group) (Author)
  • Haruhiko Koseki - , Chiba University (Author)
  • Chunaram Choudhary - , University College Copenhagen (Author)


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.


Original languageEnglish
Pages (from-to)2166-2182.e6
JournalMolecular cell
Issue number10
Publication statusPublished - 20 May 2021

External IDs

Scopus 85103990210



  • Acetylation, Animals, Biocatalysis, Chromatin/metabolism, Down-Regulation/genetics, Enhancer Elements, Genetic, Histone Deacetylases/metabolism, Histones/metabolism, Lysine/metabolism, Mice, Models, Biological, Nuclear Proteins/metabolism, Protein Binding, RNA Polymerase II/metabolism, Transcription Factor TFIID/metabolism, Transcription Factors/metabolism, Transcription Initiation, Genetic, p300-CBP Transcription Factors/metabolism