9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response

Olivier Harismendy, Dimple Notani, Xiaoyuan Song, Nazli G. Rahim, Bogdan Tanasa, Nathaniel Heintzman, Bing Ren, Xiang-Dong Fu, Eric J. Topol (), Michael G. Rosenfeld () and Kelly A. Frazer ()
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Olivier Harismendy: University of California at San Diego, School of Medicine
Dimple Notani: Howard Hughes Medical Institute, University of California at San Diego, School of Medicine
Xiaoyuan Song: Howard Hughes Medical Institute, University of California at San Diego, School of Medicine
Nazli G. Rahim: Scripps Genomic Medicine, Scripps Translational Science Institute, The Scripps Research Institute, 3344 N. Torrey Pines Court
Bogdan Tanasa: Howard Hughes Medical Institute, University of California at San Diego, School of Medicine
Nathaniel Heintzman: Ludwig Institute for Cancer Research, University of California at San Diego, School of Medicine
Bing Ren: Ludwig Institute for Cancer Research, University of California at San Diego, School of Medicine
Xiang-Dong Fu: University of California at San Diego, School of Medicine
Eric J. Topol: Scripps Genomic Medicine, Scripps Translational Science Institute, The Scripps Research Institute, 3344 N. Torrey Pines Court
Michael G. Rosenfeld: Howard Hughes Medical Institute, University of California at San Diego, School of Medicine
Kelly A. Frazer: University of California at San Diego, School of Medicine

Nature, 2011, vol. 470, issue 7333, 264-268

Abstract: Heart disease link to inflammatory signalling A non-coding region on chromosome 9p21 was previously shown to associate with coronary artery disease and type 2 diabetes, and the region has been implicated in regulating neighbouring genes. Here the authors identify 33 distinct enhancers within this region and show that single nucleotide polymorphisms in one of the enhancers affect STAT1 binding. They further show that in human vascular endothelium cells, the enhancer interval physically interacts with a number of specific loci, and that interferon-γ activation strongly affects the chromatin structure and transcriptional regulation of the 9p21 locus, including STAT1 binding, long-range enhancer interactions and expression of neighbouring genes.

Date: 2011
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DOI: 10.1038/nature09753

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