Characterization of the human renal Na+-sulphate cotransporter gene ( NAS1) promoter

Lee, Aven and Markovich, Daniel (2004) Characterization of the human renal Na+-sulphate cotransporter gene ( NAS1) promoter. Pflügers Archiv European Journal of Physiology, 448 5: 490-499. doi:10.1007/s00424-004-1251-z


Author Lee, Aven
Markovich, Daniel
Title Characterization of the human renal Na+-sulphate cotransporter gene ( NAS1) promoter
Formatted title
Characterization of the human renal Na +-sulphate cotransporter gene ( NAS1) promoter
Journal name Pflügers Archiv European Journal of Physiology   Check publisher's open access policy
ISSN 0031-6768
1432-2013
Publication date 2004-08-01
Sub-type Article (original research)
DOI 10.1007/s00424-004-1251-z
Open Access Status
Volume 448
Issue 5
Start page 490
End page 499
Total pages 10
Place of publication Berlin / Heidelberg, Germany
Publisher Springer
Language eng
Subject 11 Medical and Health Sciences
1116 Medical Physiology
17 Psychology and Cognitive Sciences
111603 Systems Physiology
111601 Cell Physiology
Abstract Sulphate (SO42-) plays an essential role during growth, development, and cellular metabolism. Recently, we have isolated the human renal Na+-SO42- cotransporter (hNaSi-1) that is implicated in the regulation of serum SO42- levels. To gain an insight into hNaSi-1 regulation, our aims were to clone and characterize functionally the hNaSi-1 gene (NAS1) promoter. We PCR-amplified 3742 bp of the NAS1 5'-flanking region, which is 64% AT-rich and contains numerous putative cis-acting elements. The NAS1 transcription start site was mapped to 25 bp upstream from the translation start site. NAS1 promoter truncations fused to luciferase gene constructs transfected into renal LLC-PK1, MDCK and OK cells allowed us to establish that the first 169 bp of the NAS1 promoter are sufficient for basal transcription. Furthermore, the NAS1 promoter conferred responsiveness to the polycyclic aromatic hydrocarbon 3-methylcholanthrene (3-MC), but not to thyroid hormone (T-3) or vitamin D [1,25-(OH)(2)D-3]. Site-directed mutagenesis of the NAS1 promoter identified a functional xenobiotic response element at -2,052, which conferred 3-MC responsiveness. The human NAS1 gene promoter is not responsive to Vitamin D or T-3, unlike the mouse Nas1 promoter with which it shares similar to40% sequence similarity, but is transactivated by 3-MC, suggesting that the control of renal SO42- reabsorption via the regulation of NAS1 transcription may be important for maintaining the sulphation potential for kidney polycyclic aromatic hydrocarbon metabolism.
Keyword Physiology
Sulphate transport
Transcriptional regulation
3-methylcholanthrene
Na+-sulphate cotransporter
Renal proximal tubule
Sulphate homeostasis
Nuclear Translocator Protein
Congenital Chloride Diarrhea
Planar aromatic-compounds
Inorganic Sulfate
Transporter Gene
Binding-site
Ah-receptor
Dna-binding
Vitamin-d
Transcriptional Regulation
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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Created: Thu, 20 Sep 2007, 03:49:20 EST