PHYLOGENETICALLY CONSERVED SEQUENCES IN THE PROMOTER OF THE RABBIT SODIUM-HYDROGEN EXCHANGER ISOFORM-1 GENE (NHE1/SLC9A1)

NHE1 (gene symbol SLC9A1) encodes an isoform of the amiloride-sensitive Na+-H+ exchanger that is present in many cells and the basolateral membrane of renal epithelia. Expression of NHE1 is modulated in response to chronic metabolic acidosis, growth factors, and phorbol eaters. To begin examining the molecular basis for this regulation, a rabbit genomic clone that contained 6 kb of 5' flanking region, the first exon, and a portion of the first intervening sequence of NHE1 was obtained. The principal transcription start site in native rabbit tissues was located 798 bp 5' to the initiation codon. The sequence of the proximal 5' flanking region of rabbit NHE1 was similar to the human sequence and contained a TATA-box, (G + C)-boxes, homopyrimidine direct repeats, and a putative AP-1 site. When ligated to luciferase and transfected into porcine renal epithelial cells (LLC-PK1), 708 bp of proximal 5' flanking region exhibited orientation-dependent promoter activity.