BRG1-SWI/SNF-dependent regulation of the Wt1 transcriptional landscape mediates epicardial activity during heart development and disease
| Autor: | Vieira, Joaquim Miguel, Howard, Sara, Villa del Campo, Cristina, Bollini, Sveva, Dubé, Karina N., Masters, Megan, Barnette, Damien N., Rohling, Mala, Sun, Xin, Hankins, Laura E., Gavriouchkina, Daria, Williams, Ruth, Metzger, Daniel, Chambon, Pierre, Sauka-Spengler, Tatjana, Davies, Benjamin, Riley, Paul R. |
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| Přispěvatelé: | University of Oxford, Great Ormond Street Institute of Child Health (UCL), University College of London [London] (UCL), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), univOAK, Archive ouverte |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Genes
Wilms Tumor Science Myocardial Infarction Mice Transgenic Article Epigenesis Genetic Mice [SDV.BDD] Life Sciences [q-bio]/Development Biology Animals Humans Regulatory Elements Transcriptional [SDV.BDD]Life Sciences [q-bio]/Development Biology Conserved Sequence Base Sequence CCAAT-Enhancer-Binding Protein-beta fungi DNA Helicases Nuclear Proteins Heart Chromatin Assembly and Disassembly Thymosin HEK293 Cells Gene Expression Regulation Pericardium Transcription Factors |
| Zdroj: | Nature Communications Nature Communications, 2017, 8, ⟨10.1038/ncomms16034⟩ Nature Communications, Vol 8, Iss 1, Pp 1-12 (2017) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms16034⟩ |
| Popis: | 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. Priming of the adult mouse heart with Tβ4 activates dormant epicardium-derived cells to aid repair of injured myocardium. Here, Vieira et al. explain this process and show that Tβ4 binds a chromatin remodeller BRG1 and activates Wt1, the key regulator of epicardial epithelial-to-mesenchymal transformation, by altering the epigenetic landscape of the Wt1 locus. |
| Databáze: | OpenAIRE |
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