A schematic representation of ligand-dependent recruitment of coactivators for PPAR-regulated target gene transcription. In the absence of ligand, the PPAR-RXR heterodimer recruits corepressors, which in turn, assemble additional components of a repressor complex including histone deacetylase (HDAC). When ligand (yellow trapezium representing PPAR ligand, and blue trapezium representing 9-cis-retinoic acid as RXR ligand) binds, conformational changes in PPAR-RXR induce dissociation of corepressor complex. Active transcriptional complex assembles with coactivator proteins either sequentially or preassembled subcomplex modules. PPAR binds to peroxisome proliferator response element (PPRE) and assemble coactivator complexes that acetylate (SRCs, p300) or methylate (CARM1) nucleosomes for chromatin remodeling. Mediator components [36, 37] contact PPARs and facilitate the recruitment of the basal transcription machinery (TATA-box-binding protein [TBP]/TBP-associated factors [TAFs]) to form linkage with RNA polymerase II for transcription of specific target genes.
