ALTERNATIVE PROMOTERS AND CARDIAC-MUSCLE CELL-SPECIFIC EXPRESSION OF THE NA+ CA2+ EXCHANGER GENE/

Many studies have investigated the regulation of the Na+/ Ca2+ exchang er, NCX1, but limited data exist on transcriptional regulation of the NCX1 gene. We have identified the transcription start sites of three t issue-specific alternative promoters of NCX1 transcripts from rat hear t, kidney, and brain. We have characterized the cardiac NCX1 promoter, from which the most abundant quantities of NCX1 transcripts are expre ssed. Transfection of primary cardiac myocytes, CHO cells, and COS-7 c ells 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 bo x, and an Inr as well as multiple active enhancers. The kidney NCX1 pr omoter has a typical TATA box and binding sites for several tissue-spe cific factors. The brain NCX1 promoter is very GC-rich and possesses s everal Sp-l binding sites consistent with its ubiquitous expression.