Hormonal Regulation of an Islet-Specific Enhancer in the Pancreatic Homeobox Gene STF-1

S Sharma, US Jhala, T Johnson, K Ferreri… - … and cellular biology, 1997 - Taylor & Francis
S Sharma, US Jhala, T Johnson, K Ferreri, J Leonard, M Montminy
Molecular and cellular biology, 1997Taylor & Francis
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-3β 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-3β activity on the islet-specific enhancer. Overexpression of HNF-3β …
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-3β 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-3β activity on the islet-specific enhancer. Overexpression of HNF-3β 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.
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