| First Author | Vieira JM | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 16034 | PubMed ID | 28737171 |
| Mgi Jnum | J:250600 | Mgi Id | MGI:5920208 |
| Doi | 10.1038/ncomms16034 | Citation | Vieira JM, et al. (2017) BRG1-SWI/SNF-dependent regulation of the Wt1 transcriptional landscape mediates epicardial activity during heart development and disease. Nat Commun 8:16034 |
| abstractText | 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. |
