THE PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR REGULATES MALIC ENZYMEGENE-EXPRESSION

A new regulatory element for peroxisome proliferator activated recepto r (PPAR)/retinoid X receptor (RXR) heterodimers was found in the promo ter of the melic enzyme gene. Similar to previously characterized pero xisome proliferator response elements (PPREs), it consists of a direct repeat of sequences related to the half-site consensus AGGTCA with an interspacing of 1 base pair. Specific binding of PPAR/RXR heterodimer s to this element was demonstrated. Furthermore, this sequence conferr ed ciprofibrate responsiveness of a reporter through the homologous ma lic enzyme or heterologous thymidine kinase promoters. This PPRE presu mably mediates the transcriptional effects of peroxisome proliferators on malic enzyme expression. The presence of a PPRE in the promoter of this lipogenic enzyme suggests a broader function for the PPAR in the regulation of lipid metabolism.