Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Basic Helix-Loop-Helix Transcription Factors
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Blotting, Northern
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Blotting, Western
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COS Cells
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DNA Footprinting
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation
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Glucocorticoids / pharmacology
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HeLa Cells
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Helix-Loop-Helix Motifs*
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Hepatocyte Nuclear Factor 3-beta
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism
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Humans
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Islets of Langerhans / metabolism*
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Molecular Sequence Data
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Trans-Activators / genetics*
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Trans-Activators / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transfection
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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FOXA2 protein, human
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Glucocorticoids
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Homeodomain Proteins
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NEUROD1 protein, human
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Nuclear Proteins
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Trans-Activators
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Transcription Factors
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pancreatic and duodenal homeobox 1 protein
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Hepatocyte Nuclear Factor 3-beta