Regulation of the mouse Nas1 promoter by vitamin D and thyroid hormone.
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 D(3) (1,25-(OH)(2)D(3)) and tri-iodothyronine (T(3)). Recently, we cloned the mouse NaS(i)-1 gene ( Nas1) and in the present study identified a 1,25-(OH)(2)D(3)- and T(3)-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 T(3)-responsive element (IR0 T(3)RE) at -436 to -425 which conferred 1,25-(OH)(2)D(3) and T(3) responsiveness, respectively. In summary, we have identified responsive elements that mediate the enhanced transcription of Nas1 by 1,25-(OH)(2)D(3) and T(3), and these mechanisms may provide important clues to the physiological control of sulfate homeostasis.
School of Biomedical Sciences, Department of Physiology and Pharmacology, University of Queensland, Brisbane 4072, St. Lucia, QLD 4072, Australia.
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D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D027682:Cation Transport Proteins; D002478:Cells, Cultured; D006706:Homeostasis / Q000502:physiology; D007668:Kidney / Q000166:cytology; D008156:Luciferases / Q000235:genetics; D051379:Mice; D009893:Opossums; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D020218:Response Elements; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates / Q000378:metabolism; D027981:Symporters / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D014284:Triiodothyronine / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D027682:Cation Transport Proteins; D012333:RNA, Messenger; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates; D027981:Symporters; D014284:Triiodothyronine; D008156:Luciferases; D002117:Calcitriol