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| Content Provider | PubMed Central |
|---|---|
| Author | Kritis, A. A. Ktistaki, E. Barda, D. Zannis, V. I. Talianidis, I. |
| 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. |
| Starting Page | 5882 |
| File Format | |
| ISSN | 13624962 |
| e-ISSN | 13624962 |
| Journal | Nucleic Acids Research |
| Issue Number | 25 |
| Volume Number | 21 |
| Language | English |
| Publisher Date | 1993-12-25 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics |
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