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Updated: Oct 1, 2025

Dissection of Enhancer Function Using Multiplex CRISPR-based Enhancer Interference in Cell Lines
Published on: June 2, 2018
Enhancer promoter interactome and Mendelian randomization identify network of druggable vascular genes in coronary
Arnaud Chignon1, Samuel Mathieu1, Anne Rufiange1
1Laboratory of Cardiovascular Pathobiology, Department of Surgery, Institut de Cardiologie Et de Pneumologie de Québec, Quebec Heart and Lung Institute/Research Center, Laval University, 2725 Chemin Ste-Foy, Québec, QC, G1V-4G5, Canada.
Abstract:
Coronary artery disease (CAD) is a multifactorial disorder, which is partly heritable. Herein, we implemented a mapping of CAD-associated candidate genes by using genome-wide enhancer-promoter conformation (H3K27ac-HiChIP) and expression quantitative trait loci (eQTL). Enhancer-promoter anchor loops from human coronary artery smooth muscle cells (HCASMC) explained 22% of the heritability for CAD. 3D enhancer-promoter genome mapping of CAD-genes in HCASMC was enriched in vascular eQTL genes. By using colocalization and Mendelian randomization analyses, we identified 58 causal candidate vascular genes including some druggable targets (MAP3K11, CAMK1D, PDGFD, IPO9 and CETP). A network analysis of causal candidate genes was enriched in TGF beta and MAPK pathways. The pharmacologic inhibition of causal candidate gene MAP3K11 in vascular SMC reduced the expression of athero-relevant genes and lowered cell migration, a cardinal process in CAD. Genes connected to enhancers are enriched in vascular eQTL and druggable genes causally associated with CAD.
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