Figure 8.

Model illustrating the repression of the PPARβ/δ target genes by TGFβ and its reversion by PPARβ/δ ligands. CoA, coactivator; CoR, corepressor; CoReg, activating or repressing coregulators; orange squares, synthetic PPARβ/δ ligand (GW501516). (Left) the absence of both GW501516 and TGFβ leads to a weak recruitment of positive and negative coregulators, resulting in a low rate of transcription. (Middle) TGFβ induces corepressor genes, including NCOR2, which leads to an enhanced recruitment of SMRT and other corepressors (CoR) to PPRE-bound PPARβ/δ complexes, and consequently an inhibition of transcription. (Bottom) GW501516 induces SMRT dissociation and favors the association with coactivators, leading to transcriptional activation. (Top) Other corepressors (CoR) induced by TGFβ, like those identified in Figure 6A, remain bound to the PPARβ/δ, resulting in a lower level of transcription compared to cells exposed to PPARβ/δ ligands in the absence of TGFβ.