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Departments of 2 Physiology and Pediatrics, 1 Division of Gastroenterology and Nutrition, UCLA School of Medicine, Los Angeles 90095-1751; and 3 Department of Biology, California State University Northridge, Northridge, California 91330
The Na+-glucose cotransporter
(SGLT1) is expressed primarily by small intestinal epithelial
cells and transports the monosaccharides glucose and galactose across
the apical membrane. Here we describe the isolation and
characterization of 5.3 kb of the 5'-flanking region of the
SGLT1 gene by transiently transfecting reporter constructs into
a variety of epithelial cell lines. A fragment (nt 
235 to +22)
of the promoter showed strong activity in the intestinal cell line
Caco-2 but was inactive in a nonintestinal epithelial 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 for maintaining the gene's basal level of
expression. The two GC boxes bind to several members of the Sp1 family
of transcription factors and, in the presence of HNF-1, synergistically
upregulate transactivation of the promoter. A novel 16-bp element just
downstream of one GC box was also shown to influence the interaction of
Sp1 to its binding site. In summary, we report the identification and
characterization of the human SGLT1 minimal promoter and the critical
role that HNF-1 and Sp1-multigene members have in enhancing the basal
level of its transcription in Caco-2 cells.
intestine; transcription; glucose-galactose malabsorption; Sp2; Sp3
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