The Mouse Sulfate Anion Transporter Gene Sat1 (Slc26a1): Cloning,Tissue Distribution,Gene Structure,Functional Characterization,and Transcriptional Regulation Thyroid Hormone

Sulfate (SO₄ ^2-) is required for bone/cartilage formation and cellular metabolism. sat-1 is a SO₄ ^2- anion transporter expressed on basolateral membranes of renal proximal tubules, and is suggested to play an important role in maintaining SO₄ ^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 SO₄ ^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 T₃REs and VDREs. We demonstrate that Sat1 promoter driven basal transcription in OK cells was stimulated by tri-iodothyronine. Site-directed mutagenesis identified an imperfect T₃RE 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 theSat1 gene encoding a SO₄ ^2-/chloride/oxalate anion transporter.