CHICKEN OVALBUMIN UPSTREAM-PROMOTER TRANSCRIPTION FACTOR (COUP-TF) COULD ACT AS A TRANSCRIPTIONAL ACTIVATOR OR REPRESSOR OF THE MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL-COA SYNTHASE GENE

The chicken ovalbumin upstream-promoter transcription factor (COUP-TF) has a dual effect on the regulation of the mitochondrial 3-hydroxy-3- methylglutaryl-CoA (HMG-CoA) synthase gene. COUP-TF could act as a tra nscriptional activator or repressor of this gene through different DNA sequences. COUP-TF induces expression of a reporter gene linked to th e mitochondrial HMG-CoA synthase gene promoter in human hepatoma HepG2 cells, but represses it in a Leydig tumour cell line (R2C); in bath t hese cell lines the expression of the mitochondrial HMG-CoA synthase g ene mimics that of liver and testis. The activation is promoted by a f ragment of the gene from coordinates -62 to +28, which contains a GC b ox and a TATA box, and where no COUP-TF binding site was observed by i n vitro DNA binding studies. On the other hand, the COUP-TF inhibitory effect is mainly due to repression of peroxisome-proliferator-activat ed receptor-dependent activation of the gene, interacting with the reg ion from -104 to -92. To our knowledge this work represents the second example of a target gene for COUP-TF I that could be either activated or repressed by the action of this receptor through different DNA seq uences of the same gene.