Coronary Artery Disease Risk Variant Dampens the Expression of CALCRL by Reducing HSF Binding to Shear Stress Responsive Enhancer in Endothelial Cells In Vitro.
coronary artery disease
coronary vessels
gene expression
genome-wide association study
polymorphism, single nucleotide
Journal
Arteriosclerosis, thrombosis, and vascular biology
ISSN: 1524-4636
Titre abrégé: Arterioscler Thromb Vasc Biol
Pays: United States
ID NLM: 9505803
Informations de publication
Date de publication:
11 Apr 2024
11 Apr 2024
Historique:
medline:
11
4
2024
pubmed:
11
4
2024
entrez:
11
4
2024
Statut:
aheadofprint
Résumé
CALCRL (calcitonin receptor-like) protein is an important mediator of the endothelial fluid shear stress response, which is associated with the genetic risk of coronary artery disease. In this study, we functionally characterized the noncoding regulatory elements carrying coronary artery disease that risks single-nucleotide polymorphisms and studied their role in the regulation of To functionally characterize the coronary artery disease single-nucleotide polymorphisms harbored around the gene We demonstrate that the regulatory element harboring rs880890 exhibits high enhancer activity and shows significant allelic bias. The A allele was favored over the G allele, particularly under shear stress conditions, mediated through alterations in the HSF1 (heat shock factor 1) motif and binding. CRISPR deletion of rs880890 enhancer resulted in downregulation of Overall, our results demonstrate the existence of an endothelial-specific HSF (heat shock factor)-regulated transcriptional enhancer that mediates
Sections du résumé
BACKGROUND
UNASSIGNED
CALCRL (calcitonin receptor-like) protein is an important mediator of the endothelial fluid shear stress response, which is associated with the genetic risk of coronary artery disease. In this study, we functionally characterized the noncoding regulatory elements carrying coronary artery disease that risks single-nucleotide polymorphisms and studied their role in the regulation of
METHODS
UNASSIGNED
To functionally characterize the coronary artery disease single-nucleotide polymorphisms harbored around the gene
RESULTS
UNASSIGNED
We demonstrate that the regulatory element harboring rs880890 exhibits high enhancer activity and shows significant allelic bias. The A allele was favored over the G allele, particularly under shear stress conditions, mediated through alterations in the HSF1 (heat shock factor 1) motif and binding. CRISPR deletion of rs880890 enhancer resulted in downregulation of
CONCLUSIONS
UNASSIGNED
Overall, our results demonstrate the existence of an endothelial-specific HSF (heat shock factor)-regulated transcriptional enhancer that mediates
Identifiants
pubmed: 38602103
doi: 10.1161/ATVBAHA.123.318964
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM