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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/H1371    most recent 01026.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Luo, X. Articles by Wang, Z. Search for Related Content PubMed PubMed Citation Articles by Luo, X. Articles by Wang, Z.

Genomic structure, transcriptional control, and tissue distribution of HERG1 and KCNQ1 genes

¹Research Center, Montreal Heart Institute, and ²Department of Medicine, University of Montreal, Montreal, Quebec, Canada; ³Department of Pharmacology, State-Province Key Laboratory of China, Hefei, Anhui; and ⁴Institute of Cardiovascular Research, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China

Submitted 5 September 2007 ; accepted in final form 7 January 2008

The long QT syndrome genes human ether-a-go-go-related gene (HERG1) and voltage-gated K⁺ channel, KQT-like subfamily, member 1, gene (KCNQ1), encoding K⁺ channels critical to the repolarization rate and repolarization reserve in cardiac cells, and thereby the likelihood of arrhythmias, are both composed of two isoforms: HERG1a and HERG1b and KCNQ1a and KCNQ1b, respectively. Expression of these genes is dynamic, depending on the differentiation status and disease states. We identified their core promoter regions and transcription start sites. Our data suggest that HERG1a and HERG1b, and KCNQ1a and KCNQ1b, represent independent transcripts instead of being alternatively spliced variants of the same gene, for they each have their own transcription start sites and their own promoter regions. We obtained data pointing to the potential role of stimulating protein 1 (Sp1) in the transactivation of these genes. We compared expression profiling of these genes across a variety of human tissues. Consistent with the general lack of cis elements for cardiac-specific transcription factors and the presence of multiple sites for ubiquitous Sp1 sites in the core promoter regions of HERG1a/HERG1b and KCNQ1a/KCNQ1b genes, the transcripts demonstrated widespread distribution across a variety of human tissues. We further revealed that the mRNA levels of all HERG1 and KCNQ1 isoforms were asymmetrically distributed within the heart, being more abundant in the right atria and ventricles relative to the left atria and ventricles. These findings open up an opportunity for studying interventricular gradients of slow and rapid delayed rectifier K⁺ current and of cardiac repolarization as well. Our study might help us understand the molecular mechanisms for arrhythmias since heterogeneity of ion channel activities is an important substrate for arrhythmogenesis.

potassium channels; promoter; transcription; human ether-a-go-go-related gene; voltage-gated potassium channel; KQT-like subfamily; member 1; stimulating protein 1

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