Background: Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor superfamily and regulate many genes of the proteins involved in lipid metabolism, including peroxisomal acyl-CoA oxidase (AOX). Through heterodimerization with retinoid X receptors (RXRs), PPAR was believed to recognize the sequence elements consisting of two directly repeating 6-bp half-sites spaced by one nucleotide (DR-1), located in the regulatory regions of these genes. Results: Employing the peroxisome proliferator-responsive enhancer of the rat AOX gene, we analysed the minimal sequence requirements for enhancer activity and PPARα/RXRα binding. We found that the sequence just downstream of the DR-1 motif is indispensable for both functions. By a direct selection procedure of high-affinity binding sites from a random sequence pool, we identified a consensus sequence at the four positions next to DR-1. We also suggest that PPARα binds to the downstream half-site, whereas RXRα binds to the upstream half-site of the AOX DR-1. Conclusions: An extended half-site of 10-bp, but not a simple 6-bp half-site, is required for the PPARα binding, upon heterodimer formation with RXRα. The binding polarity of PPARα/RXRα seems to be opposite to that of other RXR-involving heterodimers. © Blackwell Science Limited.
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Osada, S., Tsukamoto, T., Takiguchi, M., Mori, M., & Osumi, T. (1997). Identification of an extended half-site motif required for the function of peroxisome proliferator-activated receptor α. Genes to Cells, 2(5), 315–327. https://doi.org/10.1046/j.1365-2443.1997.1220319.x