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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.
Afiliación
  • Narita T; Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark.
  • Ito S; Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • Higashijima Y; Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark.
  • Chu WK; Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark.
  • Neumann K; Stem Cell Engineering, Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technische Universität Dresden, 01307 Dresden, Germany.
  • Walter J; Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark.
  • Satpathy S; Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark.
  • Liebner T; Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark.
  • Hamilton WB; The Novo Nordisk Foundation Center for Stem Cell Biology-DanStem, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
  • Maskey E; Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark.
  • Prus G; Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark.
  • Shibata M; Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • Iesmantavicius V; Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark.
  • Brickman JM; The Novo Nordisk Foundation Center for Stem Cell Biology-DanStem, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
  • Anastassiadis K; Stem Cell Engineering, Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technische Universität Dresden, 01307 Dresden, Germany.
  • Koseki H; Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; Immune Regulation, Advanced Research Departments, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
  • Choudhary C; Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark. Electronic address: chuna.choudhary@cpr.ku.dk.
Mol Cell ; 81(10): 2166-2182.e6, 2021 05 20.
Article en En | MEDLINE | ID: mdl-33765415
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Polimerasa II / Elementos de Facilitación Genéticos / Factores de Transcripción p300-CBP / Iniciación de la Transcripción Genética Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Polimerasa II / Elementos de Facilitación Genéticos / Factores de Transcripción p300-CBP / Iniciación de la Transcripción Genética Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos