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Publication : Pancreatic islet expression of the homeobox factor STF-1 relies on an E-box motif that binds USF.

First Author  Sharma S Year  1996
Journal  J Biol Chem Volume  271
Issue  4 Pages  2294-9
PubMed ID  8567692 Mgi Jnum  J:30869
Mgi Id  MGI:78445 Doi  10.1074/jbc.271.4.2294
Citation  Sharma S, et al. (1996) Pancreatic islet expression of the homeobox factor STF-1 relies on an E-box motif that binds USF. J Biol Chem 271(4):2294-9
abstractText  The commitment of cells to specific lineages during development is determined in large part by the relative expression of various homeodomain (HOX) selector proteins, which mediate the activation of distinct genetic programs. But the mechanisms by which individual HOX genes are themselves targeted for expression in different cell types remain largely uncharacterized. Here, we demonstrate that STF-1, a homeodomain protein that functions in pancreatic morphogenesis and in glucose homeostasis is encoded by an orphan homeobox gene on mouse chromosome 5. When fused to a beta-galactosidase reporter gene, a 6.5-kilobase genomic fragment of 5'-flanking sequence from the STF-1 gene shows pancreatic islet specific activity in transgenic mice. Two distinct elements within the STF-1 promoter are required for islet-restricted expression: a distal enhancer sequence located between -3 and -6.5 kilobases and a proximal E-box sequence located at -104, which is recognized primarily by the helix loop helix/leucine zipper nuclear factor USF. As point mutation within the -104 E-box that disrupt USF binding correspondingly impair STF-1 promoter activity, our results demonstrate that USF is an important component of the regulatory apparatus which directs STF-1 expression to pancreatic islet cells.
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