Chicken ovalbumin upstream promoter transcription factor (COUP-TF) binds to a peroxisome proliferator-responsive element and antagonizes peroxisome proliferator-mediated signaling.
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Peroxisome proliferators form a family of diverse xenobiotic compounds that includes hypolipidemic agents, herbicides, and plasticizers. These compounds activate transcription of a subset of nuclear genes including those encoding peroxisomal fatty acid beta-oxidation enzymes, whose 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 peroxisome proliferator-activated nuclear receptors (PPARs) that bind to upstream responsive elements (PPREs) through heterodimerization with retinoid X receptors. We demonstrate that the chicken ovalbumin upstream promoter transcription factor 1 (COUP-TF1), another member of the nuclear hormone receptor superfamily, binds to the hydratase-dehydrogenase PPRE in vitro and in vivo and antagonizes PPAR-dependent signaling. These data suggest that members of the COUP-TF family play a role in modulating receptor-mediated activation of peroxisome proliferator-responsive genes.
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