Fiche publication
Date publication
juillet 2017
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
,
Dr METZGER Daniel
Tous les auteurs :
Vieira JM, Howard S, Villa Del Campo C, Bollini S, Dubé KN, Masters M, Barnette DN, Rohling M, Sun X, Hankins LE, Gavriouchkina D, Williams R, Metzger D, Chambon P, Sauka-Spengler T, Davies B, Riley PR
Lien Pubmed
Résumé
Epicardium-derived cells (EPDCs) contribute cardiovascular cell types during development and in adulthood respond to Thymosin β4 (Tβ4) and myocardial infarction (MI) by reactivating a fetal gene programme to promote neovascularization and cardiomyogenesis. The mechanism for epicardial gene (re-)activation remains elusive. Here we reveal that BRG1, the essential ATPase subunit of the SWI/SNF chromatin-remodelling complex, is required for expression of Wilms' tumour 1 (Wt1), fetal EPDC activation and subsequent differentiation into coronary smooth muscle, and restores Wt1 activity upon MI. BRG1 physically interacts with Tβ4 and is recruited by CCAAT/enhancer-binding protein β (C/EBPβ) to discrete regulatory elements in the Wt1 locus. BRG1-Tβ4 co-operative binding promotes optimal transcription of Wt1 as the master regulator of embryonic EPDCs. Moreover, chromatin immunoprecipitation-sequencing reveals BRG1 binding at further key loci suggesting SWI/SNF activity across the fetal epicardial gene programme. These findings reveal essential functions for chromatin-remodelling in the activation of EPDCs during cardiovascular development and repair.
Mots clés
Animals, Base Sequence, CCAAT-Enhancer-Binding Protein-beta, metabolism, Chromatin Assembly and Disassembly, Conserved Sequence, DNA Helicases, metabolism, Epigenesis, Genetic, Gene Expression Regulation, Genes, Wilms Tumor, HEK293 Cells, Heart, growth & development, Humans, Mice, Mice, Transgenic, Myocardial Infarction, metabolism, Nuclear Proteins, metabolism, Pericardium, cytology, Regulatory Elements, Transcriptional, Thymosin, metabolism, Transcription Factors, metabolism
Référence
Nat Commun. 2017 Jul;8:16034
