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Publication : Tissue-specific regulation of mouse hepatocyte nuclear factor 4 expression.

First Author  Zhong W Year  1994
Journal  Mol Cell Biol Volume  14
Issue  11 Pages  7276-84
PubMed ID  7523862 Mgi Jnum  J:21334
Mgi Id  MGI:69336 Doi  10.1128/mcb.14.11.7276
Citation  Zhong W, et al. (1994) Tissue-specific regulation of mouse hepatocyte nuclear factor 4 expression. Mol Cell Biol 14(11):7276-84
abstractText  Hepatocyte nuclear factor 4 (HNF-4) is a liver-enriched transcription factor and a member of the steroid hormone receptor superfamily. HNF-4 is required for the hepatoma-specific expression of HNF-1 alpha, another liver-enriched transcription factor, suggesting the early participation of HNF-4 in development. To prepare for further study of HNF-4 in development, the tissue-specific expression of the mouse HNF-4 gene was studied by analyzing the promoter region for required DNA elements. DNase-hypersensitive sites in the gene in liver and kidney tissues were found in regions both distal and proximal to the RNA start that were absent in tissues in which HNF-4 expression did not occur. By use of reporter constructs in transient-transfection assays and with transgenic mice, a region sufficient to drive liver-specific expression of HNF-4 was identified. While an HNF-1 binding site between bp -98 and -68 played an important role in the hepatoma-specific promoter activity of HNF-4 in transient-transfection assays, it was not sufficient for the liver-specific expression of a reporter gene in transgenic mice. Distal enhancer elements indicated by the presence of DNase I-hypersensitive sites at kb -5.5 and -6.5, while not functional in transient-transfection assays, were required for the correct expression of the mouse HNF-4 gene in animals.
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