CHICKEN OVALBUMIN UPSTREAM PROMOTER TRANSCRIPTION FACTOR (COUP-TF) BINDS TO A PEROXISOME PROLIFERATOR-RESPONSIVE ELEMENT AND ANTAGONIZES PEROXISOME PROLIFERATOR-MEDIATED SIGNALING

Peroxisome proliferators form a family of diverse xenobiotic compounds that includes hypolipidemic agents, herbicides, and plasticizers. The se compounds activate transcription of a subset of nuclear genes inclu ding those encoding peroxisomal fatty acid beta-oxidation enzymes, who se elevated activities can lead to hepatocarcinogenesis. Induction of the genes encoding fatty acyl-CoA oxidase and hydratase-dehydrogenase, the first and second enzymes of the pathway, is mediated by peroxisom e proliferator-activated nuclear receptors (PPARs) that bind to upstre am responsive elements (PPREs) through heterodimerization with retinoi d X receptors. We demonstrate that the chicken ovalbumin upstream prom oter transcription factor 1 (COUP-TF1), another member of the nuclear hormone receptor superfamily, binds to the hydratase-dehydrogenase PPR E in vitro and in vivo and antagonizes PPAR-dependent signaling. These data suggest that members of the COUP-TF family play a role in modula ting receptor-mediated activation of peroxisome proliferator-responsiv e genes.