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PMID: 8290348 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

An indirect negative autoregulatory mechanism involved in hepatocyte nuclear factor-1 gene expression.

Nucleic acids research ·Vol. 21 ·No. 25 ·1993-12-25 ·Pages 5882-9

Kritis AA, Ktistaki E, Barda D, Zannis VI, 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.

Related Genes
HNF-1
MeSH Terms
Animals Apolipoprotein A-I/genetics,metabolism Apolipoprotein C-III Apolipoproteins C/genetics,metabolism 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/cytology,metabolism Molecular Sequence Data Nuclear Proteins Phosphoproteins Promoter Regions, Genetic Rats Transcription Factors/genetics,metabolism Transcriptional Activation Transfection
Chemicals
Apolipoprotein A-I Apolipoprotein C-III Apolipoproteins C Basic Helix-Loop-Helix Leucine Zipper Transcription Factors DNA-Binding Proteins HNF1A protein, human HNF1B protein, human Hepatocyte Nuclear Factor 1-alpha Hepatocyte Nuclear Factor 4 Hnf1a protein, rat MLX protein, human Nuclear Proteins Phosphoproteins Transcription Factors Hepatocyte Nuclear Factor 1 Hepatocyte Nuclear Factor 1-beta DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kritis A A
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Crete, Greece.
Ktistaki E
Barda D
Zannis V I
Talianidis I
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/21.25.5882
Published
1993-12-25
Pages
5882-9
Language
English
Region
England
NLM ID
0411011
PMCID
PMC310469
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/21.25.5882 PMC Full Text View journal details
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