A Promoter in the Novel Exon of hPPAR gamma Directs the Circadian Expression of PPAR gamma

Aim: PPAR gamma (peroxisome proliferator-activated receptor gamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors that regulate the expression of genes associated with lipid metabolism. Herein, we show that expression levels of the novel PPAR gamma transcript exhibit circadian oscillation. To study the mechanisms controlling PPAR gamma expression, a novel PPAR gamma gene promoter was cloned and characterized. Methods: We analyzed the novel PPAR gamma promoter by luciferase reporter assays and gel shift analysis. Results: Surprisingly, it was not an intron but rather the novel first exon of PPAR gamma that was found to have functional minimal promoter activity. Luciferase reporter assays and gel shift assays revealed that the novel first exon is essential for novel PPAR gamma promoter activation and that DBP (albumin gene D-site binding protein) and E4BP4 (E4 promoter A binding protein 4) bind directly to D-sites in the novel first exon. Conclusion: Our results demonstrate that the PAR-bZIP (bZIP, basic leucine zipper) family and E4BP4 are the main regulatory factors involved in oscillation of novel PPAR gamma expression. This regulatory mechanism clearly differs from that of the circadian expression of PPAR alpha.