PPARγ-RXR nuclear receptor complex and transcriptional activity (activation)

Coactivator protein

Ligand

PPARγ

RXRα

Ligand

DNA

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.

PPRE

Corepressor protein

Mutant PPARγ

RXR

DNA

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.

PPARγ-RXR nuclear receptor complex and transcriptional activity (inhibition)

PPRE