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. |