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

Acetylation Acylation Cell Cycle Proteins / metabolism Cell Line, Tumor Chromatin / metabolism Fatty Acids / biosynthesis Female Gene Expression Regulation, Leukemic Genome, Human Histones / metabolism Humans Lysine / metabolism Mitochondria / metabolism Mitochondrial Proteins / metabolism Models, Biological Oxidation-Reduction Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics Protein Binding Protein Processing, Post-Translational RNA-Binding Proteins / metabolism Transcription Factors / metabolism

Journal

Cell reports

ISSN: 2211-1247

Titre abrégé: Cell Rep

Pays: United States

ID NLM: 101573691

Informations de publication

Date de publication:
27 07 2021

Historique:

received: 04 01 2021

revised: 11 05 2021

accepted: 08 07 2021

entrez: 28 7 2021

pubmed: 29 7 2021

medline: 10 2 2022

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2021.109460 PMID: 34320364

pubmed: 34320364

pii: S2211-1247(21)00883-4

doi: 10.1016/j.celrep.2021.109460

pii:

doi:

Substances chimiques

BRD4 protein, human 0

Cell Cycle Proteins 0

Chromatin 0

FASTKD1 protein, human 0

Fatty Acids 0

Histones 0

Mitochondrial Proteins 0

RNA-Binding Proteins 0

Transcription Factors 0

Lysine K3Z4F929H6

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

109460

Informations de copyright

Déclaration de conflit d'intérêts

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.