PPAR γ -RXR nuclear receptor complex and transcriptional activity (activation)

1.  Addition of ligand (L) to the DNA-bound PPARγ-RXR heterodimer promotes recruitment of a transcriptional 'coactivator' protein complex, which in turn modulates the transcription of target genes regulating different physiological processes. (c) Dominant negative human PPARγ mutants retain the ability to heterodimerize with RXR on DNA, but fail to bind ligand and recruit transcriptional coactivators. Instead they recruit a 'corepressor' protein complex, leading to silencing of target gene transcription. PPRE, PPAR response element; BTFs, basal transcription factors. PPARγ-RXR nuclear receptor complex and transcriptional activity (activation) Coactivator protein Ligand PPARγ RXRα Ligand DNA PPRE PPARγ forms a heterodimer with RXR (PPARγ-RXR Complex) to bind to DNA. If ligand binds to either PPAR or RXR, changes in the heterodimer are induced which lead to the release of corepressor molecules and the recruitment of coactivator proteins resulting in the formation of a transcriptional regulatory complex as shown above. This complex then binds to specific PPAR response elements (PPRE) resulting in transcriptional activation of target genes, regulating physiological processes such as adipocyte differentiation, glucose homeostasis, anti-inflammation etc.

2. PPARγ-RXR nuclearreceptorcomplexandtranscriptionalactivity (inhibition) Corepressor protein Mutant PPARγ RXR DNA PPRE Human PPARγ mutants are able to heterodimerise with RXR on DNA but cannot bind ligand. This leads to the recruitment of a corepressor instead of a coactivator protein leading to silencing of target gene transcription.