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• W2123308455 startingPage "7186" @default.
• W2123308455 abstract "The proglucagon gene is expressed in a highly restricted tissue-specific manner in the α cells of the pancreatic islet, the hypothalamus, and the small and large intestines. Proglucagon is processed to glucagon and glucagon-like peptides GLP-1 and -2. Glucagon is expressed in α cells and regulates glucose homeostasis. GLP-1 is implicated in the control of insulin secretion, food intake, and satiety signaling, and GLP-2 is implicated in regulating small-bowel growth. Cell-specific expression of the proglucagon gene is mediated by proteins that interact with the proximal G1 promoter element which contains several AT-rich domains with binding sites for homeodomain transcription factors. In an attempt to identify major homeodomain proteins involved in pancreatic α-cell-specific proglucagon expression, we found that the POU domain transcription factor brain 4 is abundantly expressed in proglucagon-producing islet cell lines and rat pancreatic islets. In the latter, brain 4 and glucagon immunoreactivity colocalize in the outer mantle of islets. Electrophoretic mobility shift assays with specific antisera identify brain 4 as a major constituent of nuclear proteins of glucagon-producing cells that bind to the G1 element of the proglucagon gene proximal promoter. Transcriptional transactivation experiments reveal that brain 4 is a major regulator of proglucagon gene expression by its interaction with the G1 element. The finding that a neuronal transcription factor is involved in glucagon gene transcription may explain the presence of proglucagon in certain areas of the brain as well as in pancreatic α cells. Further, this finding supports the idea that the neuronal properties of endodermis-derived endocrine pancreatic cells may find their basis in regulation of gene expression by neuronal transcription factors." @default.
• W2123308455 created "2016-06-24" @default.
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• W2123308455 date "1997-12-01" @default.
• W2123308455 modified "2023-10-18" @default.
• W2123308455 title "POU Domain Transcription Factor brain 4 Confers Pancreatic α-Cell-Specific Expression of the Proglucagon Gene Through Interaction with a Novel Proximal Promoter G1 Element" @default.
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• W2123308455 doi "https://doi.org/10.1128/mcb.17.12.7186" @default.
• W2123308455 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/232576" @default.
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