PPAR alpha mediates peroxisome proliferator-induced transcriptional repression of nonperoxisomal gene expression in mouse.

The strain difference, peroxisome proliferator specificity and role of PPAR alpha in peroxisome proliferator-induced transcriptional repression of nonperoxisomal transthyretin and alpha2u-globulin genes were examined. The genes were repressed by four peroxisome proliferators in all seven mouse strains tested. The extent of repression was strongly dependent on both the mouse strains and type of proliferator, although the mRNA levels of PPAR alpha and its partner in heterodimerization, RXR alpha were not different. The role of PPAR alpha in repression was confirmed by the finding that PPAR alpha-null mice were not responsive to transcriptional repression. These results indicate that PPAR alpha plays an obligatory role in transcription of various genes, some of which are not related to lipid metabolism.