The mouse sulfate anion transporter gene Sat1 (Slc26a1): cloning, tissue distribution, gene structure, functional characterization, and transcriptional regulation thyroid hormone.
Sulfate (SO(4)(2-)) is required for bone/cartilage formation and cellular metabolism. sat-1 is a SO(4)(2-) anion transporter expressed on basolateral membranes of renal proximal tubules, and is suggested to play an important role in maintaining SO(4)(2-) homeostasis. As a first step towards studying its tissue-specific expression, hormonal regulation, and in preparation for the generation of knockout mice, we have cloned and characterized the mouse sat-1 cDNA (msat-1), gene (sat1; Slc26a1) and promoter region. msat-1 encodes a 704 amino acid protein (75.4 kDa) with 12 putative transmembrane domains that induce SO(4)(2-) (also oxalate and chloride) transport in Xenopus oocytes. msat-1 mRNA was expressed in kidney, liver, cecum, calvaria, brain, heart, and skeletal muscle. Two distinct transcripts were expressed in kidney and liver due to alternative utilization of the first intron, corresponding to an internal portion of the 5'-untranslated region. The Sat1 gene (~6 kb) consists of 4 exons. Its promoter is ~52% G + C rich and contains a number of well-characterized cis-acting elements, including sequences resembling hormone responsive elements T(3)REs and VDREs. We demonstrate that Sat1 promoter driven basal transcription in OK cells was stimulated by tri-iodothyronine. Site-directed mutagenesis identified an imperfect T(3)RE at -454-bp in the Sat1 promoter to be responsible for this activity. This study represents the first characterization of the structure and regulation of the Sat1 gene encoding a SO(4)(2-)/chloride/oxalate anion transporter.
Lee
Aven
A
Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.
Beck
Laurent
L
Markovich
Daniel
D
D024506:5' Flanking Region / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins; D017920:Antiporters / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D000076988:Sulfate Transporters; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000378:metabolism*
D027321:Anion Transport Proteins; D017920:Antiporters; C466903:Slc26a1 protein, mouse; D000076988:Sulfate Transporters; D014157:Transcription Factors; D014284:Triiodothyronine