BRG1-SWI/SNF-dependent regulation of the Wt1 transcriptional landscape mediates epicardial activity during heart development and disease - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2017

BRG1-SWI/SNF-dependent regulation of the Wt1 transcriptional landscape mediates epicardial activity during heart development and disease

Résumé

Epicardium-derived cells (EPDCs) contribute cardiovascular cell types during development and in adulthood respond to Thymosin beta4 (Tbeta4) 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 Tbeta4 and is recruited by CCAAT/enhancer-binding protein beta (C/EBPbeta) to discrete regulatory elements in the Wt1 locus. BRG1-Tbeta4 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.

Dates et versions

hal-03676413 , version 1 (23-05-2022)

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Citer

Joaquim Vieira, Sara Howard, Cristina Villa del Campo, Sveva Bollini, Karina Dubé, et al.. BRG1-SWI/SNF-dependent regulation of the Wt1 transcriptional landscape mediates epicardial activity during heart development and disease. Nature Communications, 2017, 8, ⟨10.1038/ncomms16034⟩. ⟨hal-03676413⟩
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