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Am J Physiol Heart Circ Physiol 274: H217-H232, 1998;
0363-6135/98 $5.00
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Vol. 274, Issue 1, H217-H232, January 1998

Alternative promoters and cardiac muscle cell-specific expression of the Na+/Ca2+ exchanger gene

Susanne B. Nicholas1, Weidong Yang2, Shwu-Luan Lee3, Hong Zhu1, Kenneth D. Philipson1, and Jonathan Lytton2

1 Departments of Physiology and Medicine and the Cardiovascular Research Laboratories, University of California, Los Angeles, School of Medicine, Los Angeles, California 90095-1760; 2 Department of Medical Biochemistry, Health Sciences Center, University of Calgary, Alberta, Canada T2N4N1; and 3 Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Massachusetts 02115

Many studies have investigated the regulation of the Na+/Ca2+ exchanger, NCX1, but limited data exist on transcriptional regulation of the NCX1 gene. We have identified the transcription start sites of three tissue-specific alternative promoters of NCX1 transcripts from rat heart, kidney, and brain. We have characterized the cardiac NCX1 promoter, from which the most abundant quantities of NCX1 transcripts are expressed. Transfection of primary cardiac myocytes, CHO cells, and COS-7 cells with overlapping genomic DNA fragments spanning the NCX1 cardiac transcription start site has uncovered a cardiac cell-specific minimum promoter from -137 to +85. The cardiac NCX1 promoter is TATA-less but has putative binding sites for cardiac-specific GATA factors, an E box, and an Inr as well as multiple active enhancers. The kidney NCX1 promoter has a typical TATA box and binding sites for several tissue-specific factors. The brain NCX1 promoter is very GC-rich and possesses several Sp-1 binding sites consistent with its ubiquitous expression.

transcription start sites; cardiac myocytes; genetic regulation; enhancers; transcription factors


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