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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/7341
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| Title: | Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus |
| Authors: | Miller, CL;Anderson, DR;Kundu, RK;Raiesdana, A;Nürnberg, ST;Diaz, R;Cheng, K;Leeper, NJ;Chen, CH;Chang, IS;Schadt, EE;Hsiung, CA;Assimes, TL;Quertermous, T |
| Contributors: | Division of Biostatistics and Bioinformatics |
| Abstract: | Coronary heart disease (CHD) is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS) have now identified 46 independent susceptibility loci for CHD, however, the biological and disease-relevant mechanisms for these associations remain elusive. The large-scale meta-analysis of GWAS recently identified in Caucasians a CHD-associated locus at chromosome 6q23.2, a region containing the transcription factor TCF21 gene. TCF21 (Capsulin/Pod1/Epicardin) is a member of the basic-helix-loop-helix (bHLH) transcription factor family, and regulates cell fate decisions and differentiation in the developing coronary vasculature. Herein, we characterize a cis-regulatory mechanism by which the lead polymorphism rs12190287 disrupts an atypical activator protein 1 (AP-1) element, as demonstrated by allele-specific transcriptional regulation, transcription factor binding, and chromatin organization, leading to altered TCF21 expression. Further, this element is shown to mediate signaling through platelet-derived growth factor receptor beta (PDGFR-β) and Wilms tumor 1 (WT1) pathways. A second disease allele identified in East Asians also appears to disrupt an AP-1-like element. Thus, both disease-related growth factor and embryonic signaling pathways may regulate CHD risk through two independent alleles at TCF21. |
| Date: | 2013-07-18 |
| Relation: | PLoS Genetics. 2013 Jul 18;9(7):Article number e1003652. |
| Link to: | http://dx.doi.org/10.1371/journal.pgen.1003652 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1553-7404&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000322321100049 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84880779995 |
| Appears in Collections: | [熊昭] 期刊論文
[張憶壽] 期刊論文
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| PLO2013080112.pdf | | 3692Kb | Adobe PDF | 484 | View/Open |
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