The Hepatocyte Nuclear Factor 4 (HNF-4) Represses the Mitochondrial HMG-CoA Synthase Gene

We have recently shown that the gene for the mitochondrial HMG-CoA synthase is a target for PPAR and that this receptor mediates the induction of this gene by fatty acids. With the aim of gaining further insight into the function and regulation of this gene we examined the effect of other members of...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1998-01, Vol.242 (3), p.692-696
Main Authors: Rodrı&#x0301, guez, Joan C., Ortiz, José A., Hegardt, Fausto G., Haro, Diego
Format: Article
Language:English
Subjects:
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Chloramphenicol O-Acetyltransferase - genetics
Chloramphenicol O-Acetyltransferase - metabolism
DNA-Binding Proteins - analysis
DNA-Binding Proteins - metabolism
Electrophoresis, Polyacrylamide Gel
Gene Expression Regulation - genetics
Genes, Reporter
Hepatocyte Nuclear Factor 4
Humans
Hydroxymethylglutaryl-CoA Synthase - genetics
Mitochondria, Liver - enzymology
Nuclear Proteins - metabolism
Oligodeoxyribonucleotides - chemistry
Oligodeoxyribonucleotides - metabolism
Phosphoproteins - metabolism
Promoter Regions, Genetic - genetics
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Retinoic Acid - metabolism
Repressor Proteins - metabolism
Retinoid X Receptors
Transcription Factors - metabolism
Transfection - genetics
Tumor Cells, Cultured
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Summary:We have recently shown that the gene for the mitochondrial HMG-CoA synthase is a target for PPAR and that this receptor mediates the induction of this gene by fatty acids. With the aim of gaining further insight into the function and regulation of this gene we examined the effect of other members of the nuclear hormone receptor superfamily on its expression. We previously identified a regulatory element in the mitochondrial HMG-CoA synthase gene promoter that confers transcriptional regulation by PPAR, RXR and the orphan nuclear receptor COUP-TF. In this study we demonstrate a trans-repressing regulatory function for HNF-4 at this same nuclear receptor response element (NRRE). HNF-4 binds to the mitochondrial HMG-CoA synthase NRRE, and, in cotransfection assays in HepG2 cells, it represses PPAR-dependent activation of a reporter gene linked to the mitochondrial HMG-CoA synthase gene promoter.These results suggest that the mitochondrial HMG-CoA synthase gene is subject to differential regulation by the interplay of multiple members of the nuclear hormone receptor superfamily.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1997.8032