Jc. Rodriguez et al., THE HEPATOCYTE NUCLEAR FACTOR-4 (HNF-4) REPRESSES THE MITOCHONDRIAL HMG-COA SYNTHASE GENE, Biochemical and biophysical research communications, 242(3), 1998, pp. 692-696
We have recently shown that the gene for the mitochondrial HMG-CoA syn
thase is a target for PPAR and that this receptor mediates the inducti
on of this gene by fatty acids. With the aim of gaining further insigh
t into the function and regulation of this gene we examined the effect
of other members of the nuclear hormone receptor superfamily on its e
xpression. We previously identified a regulatory element in the mitoch
ondrial HMG-CoA synthase gene promoter that confers transcriptional re
gulation 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 assay
s in HepG2 cells, it represses PPAR-dependent activation of a reporter
gene linked to the mitochondrial HMG-CoA synthase gene promoter. Thes
e results suggest that the mitochondrial HMG-CoA synthase gene is subj
ect to differential regulation by the interplay of multiple members of
the nuclear hormone receptor superfamily. (C) 1998 Academic Press.