Regulation of the mouse Nas1 promoter by vitamin D and thyroid hormone

Abstract.

The renal sodium-sulfate cotransporter, NaS_i-1, a protein implicated to control serum sulfate levels, has been shown to be regulated in vivo by 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃) and tri-iodothyronine (T₃). Recently, we cloned the mouse NaS_i-1 gene (Nas1) and in the present study identified a 1,25-(OH)₂D₃- and T₃-responsive element located within the Nas1 promoter. 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 (IR0 T₃RE) at –436 to –425 which conferred 1,25-(OH)₂D₃ and T₃ responsiveness, respectively. In summary, we have identified responsive elements that mediate the enhanced transcription of Nas1 by 1,25-(OH)₂D₃ and T₃, and these mechanisms may provide important clues to the physiological control of sulfate homeostasis.