Figure 4. Model for BET protein co-repression of PPARγ-responsive genes.
Transcriptional co-repression of specific loci is an active process that requires the recruitment of repressor complexes. In the case of peroxisome proliferator-activated receptor-γ (PPARγ), co-repression is enabled through BRD2 association with RXR, which is known to heterodimerize with PPARγ. Removal of BRD2 by genetic ablation promotes the transcription of adipogenic networks118, analogous to thiazolidinedione drug treatment. Small-molecule inhibitors of BET proteins would be expected to produce a similar result.