An indirect negative autoregulatory mechanism involved in hepatocyte nuclear factor-1 gene expression.
Τίτλος | An indirect negative autoregulatory mechanism involved in hepatocyte nuclear factor-1 gene expression. |
Publication Type | Journal Article |
Year of Publication | 1993 |
Authors | Kritis, A. A., Ktistaki E., Barda D., Zannis V. I., & Talianidis I. |
Journal | Nucleic Acids Res |
Volume | 21 |
Issue | 25 |
Pagination | 5882-9 |
Date Published | 1993 Dec 25 |
ISSN | 0305-1048 |
Λέξεις κλειδιά | Animals, Apolipoprotein A-I, Apolipoprotein C-III, Apolipoproteins C, Base Sequence, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Binding Sites, Cell Line, DNA, DNA-Binding Proteins, Down-Regulation, Feedback, Gene Expression Regulation, HeLa Cells, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Hepatocyte Nuclear Factor 4, Humans, Liver, Molecular Sequence Data, Nuclear Proteins, Phosphoproteins, Promoter Regions, Genetic, Rats, Transcription Factors, Transcriptional Activation, Transfection |
Abstract | Recent studies have revealed that hepatocyte nuclear factor 4 (HNF-4) is an essential positive regulator of another liver enriched transcription factor HNF-1, defining a transcriptional hierarchy between the two factors operating in hepatocytes. To assess the possible autoregulation of the HNF-1 gene we have examined the effect of HNF-1 on its own transcription. In transient transfection assays, HNF-1 strongly down-regulated transcription driven by its own promoter in HepG2 cells. In addition HNF-1 also repressed the activity of HNF-4 dependent ApoCIII and ApoAI promoters. The same effect was observed using vHNF-1, a distinct but highly related protein to HNF-1. Both HNF-1 and vHNF-1 downregulated HNF-4 activated transcription from intact and chimeric promoter constructs carrying various HNF-4 binding sites implying that they act by impeding HNF-4 binding or activity. DNA binding and cell free transcription experiments however failed to demonstrate any direct or indirect interaction of HNF-1 and vHNF-1 with the above regulatory regions. Both factors repressed HNF-4 induced transcription of the ApoCIII and HNF-1 genes in HeLa cells, arguing against the requirement of a hepatocyte specific function. These findings define an indirect negative autoregulatory mechanism involved in HNF-1 gene expression, which in turn may affect HNF-4 dependent transcription of other liver specific genes. |
DOI | 10.1093/nar/21.25.5882 |
Alternate Journal | Nucleic Acids Res |
PubMed ID | 8290348 |
PubMed Central ID | PMC310469 |