Metabolically controlled histone H4K5 acylation/acetylation ratio drives BRD4 genomic distribution.

Autor:	Gao M; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China., Wang J; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China., Rousseaux S; CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China., Tan M; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, 201203 Shanghai, China., Pan L; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, 201203 Shanghai, China., Peng L; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China., Wang S; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China., Xu W; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China., Ren J; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China., Liu Y; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China., Spinck M; Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany., Barral S; CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China., Wang T; CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China., Chuffart F; CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China., Bourova-Flin E; CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China., Puthier D; Aix Marseille Université, INSERM, TAGC, TGML, 13288 Marseille, France., Curtet S; CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China., Bargier L; Aix Marseille Université, INSERM, TAGC, TGML, 13288 Marseille, France., Cheng Z; Jingjie PTM Biolab (Hangzhou), 310018 Hangzhou, China., Neumann H; Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany., Li J; Clinical Research Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China., Zhao Y; Ben May Department of Cancer Research, The University of Chicago, Chicago, IL 60637, USA., Mi JQ; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China. Electronic address: jianqingmi@shsmu.edu.cn., Khochbin S; CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China. Electronic address: saadi.khochbin@univ-grenoble-alpes.fr.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Jul 27; Vol. 36 (4), pp. 109460.
DOI:	10.1016/j.celrep.2021.109460
Abstrakt:	In addition to acetylation, histones are modified by a series of competing longer-chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions hinder our understanding of histone acylations' specific roles. Here, by using an acute lymphoblastic leukemia (ALL) cell model and blasts from individuals with B-precusor ALL (B-ALL), we demonstrate a role of mitochondrial activity in controlling the histone acylation/acetylation ratio, especially at histone H4 lysine 5 (H4K5). An increase in the ratio of non-acetyl acylations (crotonylation or butyrylation) over acetylation on H4K5 weakens bromodomain containing protein 4 (BRD4) bromodomain-dependent chromatin interaction and enhances BRD4 nuclear mobility and availability for binding transcription start site regions of active genes. Our data suggest that the metabolism-driven control of the histone acetylation/longer-chain acylation(s) ratio could be a common mechanism regulating the bromodomain factors' functional genomic distribution. Competing Interests: Declaration of interests Y.Z. is a founder, board member, advisor to, and inventor on patents licensed to PTM Biolabs Inc. (Hangzhou, China and Chicago, IL) and Maponos Therapeutics Inc. (Chicago, IL). Z.C. is an employee and equity holder of PTM BioLabs Inc. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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