Back to Search
Start Over
Cardiac cell type-specific gene regulatory programs and disease risk association.
- Source :
- Science advances; vol 7, iss 20, eabf1444; 2375-2548
- Publication Year :
- 2021
-
Abstract
- Misregulated gene expression in human hearts can result in cardiovascular diseases that are leading causes of mortality worldwide. However, the limited information on the genomic location of candidate cis-regulatory elements (cCREs) such as enhancers and promoters in distinct cardiac cell types has restricted the understanding of these diseases. Here, we defined >287,000 cCREs in the four chambers of the human heart at single-cell resolution, which revealed cCREs and candidate transcription factors associated with cardiac cell types in a region-dependent manner and during heart failure. We further found cardiovascular disease-associated genetic variants enriched within these cCREs including 38 candidate causal atrial fibrillation variants localized to cardiomyocyte cCREs. Additional functional studies revealed that two of these variants affect a cCRE controlling KCNH2/HERG expression and action potential repolarization. Overall, this atlas of human cardiac cCREs provides the foundation for illuminating cell type-specific gene regulation in human hearts during health and disease.
Details
- Database :
- OAIster
- Journal :
- Science advances; vol 7, iss 20, eabf1444; 2375-2548
- Notes :
- application/pdf, Science advances vol 7, iss 20, eabf1444 2375-2548
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1287297496
- Document Type :
- Electronic Resource