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.
Dawson
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PA
School of Biomedical Sciences, Department of Physiology and Pharmacology, University of Queensland, Brisbane 4072, St. Lucia, QLD 4072, Australia.
Markovich
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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