Fig. 2.

Mechanisms of genetic regulation by PPARs. (A) Upon ligand binding, PPARs induce gene expression. A subset of the induction, shown here, is the result of the direct regulation of gene expression by transactivation. Liganded PPAR/RXR heterodimers recruit co-activator molecules to promoters that contain PPAR response elements and subsequently activate gene expression. (B) A subset of direct target genes might be repressed by PPARs in the presence of ligands. However, the majority of characterized PPAR-mediated transcriptional regulations result in activation. (C) Ligand dependent trans-repression by PPARs. Upon ligand binding, PPARs can interfere with the activity of distinct transcription factors, such as NF-κB, through protein–protein interactions. (D) Ligand independent transrepression. Unliganded PPARs can bind and sequester transcription factors blocking their activity. A typical example for such a mechanism is the binding of BCL-6 by unliganded PPARβ/δ. (E) PPARs alter systemic lipid homeostasis which can affect gene regulation through unrelated transcription factors.