Transcriptional regulation of the sodium-sulfate cotransporter NaS(i)-1 gene.

Inorganic sulfate is one of the most abundant anions in mammalian plasma and is essential for proper cell growth and development, as well as detoxification and activation of many biological compounds. To date, little is understood how physiological levels of sulfate are maintained in the body. Our studies, and of others, have identified the NAS(i)-1 protein to be a functional sulfate transporter in the kidney and intestine, and due to this localization, constitutes a strong candidate gene for maintaining body sulfate homeostasis. Several factors, including hormones and metabolic conditions, have been shown to alter NAS(i)-1 mRNA and protein levels in vivo. In this study, we describe the transcriptional regulation of NaS(i)-1, with a focus on the mouse NaS(i)-1 gene (Nas1) that was recently cloned in our laboratory. Vitamin D (1,25-(OH)2D3) and thyroid hormone (T3) led to an increase in Nas1 promoter activity in OK cells. Mutational analysis of the Nas1 promoter resulted in identification of a direct repeat 6-type vitamin-D-responsive element (DR6 VDRE) at -525 to -508 and an imperfect inverted repeat 0-type T3 responsive element (IRO T3RE) at -426 to -425 which conferred 1,25-(OH)2D3 and T3 responsiveness respectively. These findings suggest for vitamin D and thyroid hormone regulation of NaS(i)-1, may provide important clues to the physiological control of sulfate homeostasis.