Atlas of cardiac endothelial cell enhancer elements linking the mineralocorticoid receptor to pathological gene expression
Abstract: Endothelial cells play crucial roles in physiology and are increasingly recognized as therapeutic targets in cardiovascular disease. Here, we analyzed the regulatory landscape of cardiac endothelial cells by assessing chromatin accessibility, histone modifications, and 3D chromatin organization and confirmed the functional relevance of enhancer-promoter interactions by CRISPRi-mediated enhancer silencing. We used this dataset to explore mechanisms of transcriptional regulation in cardiovascular disease and compared six different experimental models of heart failure, hypertension, or diabetes. Enhancers that regulate gene expression in diseased endothelial cells were enriched with binding sites for a distinct set of transcription factors, including the mineralocorticoid receptor (MR), a known drug target in heart failure and hypertension. For proof of concept, we applied endothelial cell–specific MR deletion in mice to confirm MR-dependent gene expression and predicted direct MR target genes. Overall, we have compiled here a comprehensive atlas of cardiac endothelial cell enhancer elements that provides insight into the role of transcription factors in cardiovascular disease
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Science advances. - 10, 10 (2024) , eadj5101, ISSN: 2375-2548
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2024
- DOI
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10.1126/sciadv.adj5101
- URN
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urn:nbn:de:bsz:25-freidok-2459413
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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25.03.2025, 1:50 PM CET
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
Time of origin
- 2024
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Mechanismen distaler Enhancer
Mechanisms of enhancer regulation
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Crosstalk of macrophages and endothelial cells in endothelial-to-mesenchymal transition and cardiac fibrosis
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Mode of action of the mitochondrial Ca2+ uptake enhancer efsevin for treatment of cardiac arrhythmia
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Mechanismen distaler Enhancer
Mechanisms of enhancer regulation
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Crosstalk of macrophages and endothelial cells in endothelial-to-mesenchymal transition and cardiac fibrosis
Why is endothelial resilience key to maintain cardiac health?
Optimization of a mitochondrial calcium uptake enhancer for the treatment of cardiac arrhythmia
Histone deacetylase 6 inhibitor JS28 prevents pathological gene expression in cardiac myocytes
Role of endothelial cell-derived WNT ligands in controlling physiological and pathological angiogenesis
Angiogenic endothelial cell signaling in cardiac hypertrophy and heart failure
Gene expression in immortalized versus primary isolated cardiac endothelial cells
Mode of action of the mitochondrial Ca2+ uptake enhancer efsevin for treatment of cardiac arrhythmia
Analysis of the effects of ketone bodies on cardiac endothelial cells
Mechanismen distaler Enhancer