The peroxisome proliferator activated receptor regulates malic enzyme gene expression

Abstract

A new regulatory element for peroxisome proliferator activated receptor (PPAR)/retinoid X receptor (RXR) heterodimers was found in the promoter of the malic enzyme gene. Similar to previously characterized peroxisome 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 heterodimers to this element was demonstrated. Furthermore, this sequence conferred ciprofibrate responsiveness of a reporter through the homologous malic enzyme or heterologous thymidine kinase promoters. This PPRE presumably 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.