Peroxisome proliferators-activated receptors (PPARs) are ligand inducible transcription factors of the nuclear receptor superfamily, capable of acting as co-repressors and/or co-activators for gene expression. Nuclear receptors contain a series of conserved domains or regions. These domains/regions include a variable NH2-domain (A/B region), a conserved DNA-binding domain (DBD or region C), a linker region (region D), a ligand binding domain (LBD or region E), and in some receptors a variable COOH-terminal (region F).
Three distinct subtypes of PPARs include PPAR alpha, PPAR delta and PPAR gamma, respectively. All PPAR subfamily members heterodimerize with the receptor for 9-cis retinoic acid (RXR) and bind to target gene peroxisome proliferators elements (PPREs), a direct repeat of the sequence AGGTCA separated by one nucleotide (DR-1). Although the function of PPAR delta, which is expressed ubiquitously, is less well known, this subtype may be involved in the regulation of cholesterol and lipid metabolism, in keratinocyte proliferation and in apoptosis. Among the three PPARs, PPAR delta distinguished itself by displaying remarkably potent transcriptional repression activity. Agonist binding to PPAR delta ligand binding domain provokes a conformational change that produces a suitable binding surface for recruitment of coactivators. These conformational changes lead to a decrease in the affinity of transcription co-repressors and the interaction with transcription co-activators. These co-activators and co-repressors regulate gene transcription by interacting with the transcriptional pre-initiation complex and histone acetyl transferases.