Regulation of the human Na+-glucose cotransporter gene, SGLT1, by HNF-1 and Sp1

The Na+-glucose cotransporter (SGLT1) is expressed primarily by small intes tinal epithelial cells and transports the monosaccharides glucose and galac tose across the apical membrane. Here we describe the isolation and charact erization of 5.3 kb of the 5'-flanking region of the SGLT1 gene by transien tly transfecting reporter constructs into a variety of epithelial cell line s. A fragment (nt -235 to +22) of the promoter showed strong activity in th e intestinal cell line Caco-2 but was inactive in a nonintestinal epithelia l cell line (Chinese hamster ovary). Within this region, three cis-elements , a hepatocyte nuclear factor-1 (HNF-1) and two GC box sites are critical f or maintaining the gene's basal level of expression. The two GC boxes bind to several members of the Spl family of transcription factors and, in the p resence of HNF-1, synergistically upregulate transactivation of the promote r. A novel 16-bp element just downstream of one GC box was also shown to in fluence the interaction of Spl to its binding site. In summary, we report t he identification and characterization of the human SGLT1 minimal promoter and the critical role that HNF-1 and Spl-multigene members have in enhancin g the basal level of its transcription in Caco-2 cells.