Hormonal regulation of an islet-specific enhancer in the pancreatic homeobox gene STF-1.
The homeobox protein STF-1 appears to function as a master control switch for expression of the pancreatic program during development. Here we characterize a composite enhancer which directs STF-1 expression to pancreatic islet cells via two functional elements that recognize the nuclear factors HNF-3beta and BETA-2. In keeping with their inhibitory effects on islet cell maturation, glucocorticoids were found to repress STF-1 gene expression by interfering with HNF-3beta activity on the islet-specific enhancer. Overexpression of HNF-3beta suppressed glucocorticoid receptor-mediated inhibition of the STF-1 gene, and our results suggest that the expansion of pancreatic islet precursor cells during development may be restricted by hormonal cues which regulate STF-1 gene expression.
Sharma
S
S
Department of Biology, University of California, San Diego, La Jolla 92037, USA.
Jhala
U S
US
Johnson
T
T
Ferreri
K
K
Leonard
J
J
Montminy
M
M
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D006367:HeLa Cells; D018257:Helix-Loop-Helix Motifs; D051542:Hepatocyte Nuclear Factor 3-beta; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D051542:Hepatocyte Nuclear Factor 3-beta; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C496502:FOXA2 protein, human; C093970:NEUROD1 protein, human; C084010:pancreatic and duodenal homeobox 1 protein