p300 interacts with the N- and C-terminal part of PPARγ2 in a ligand-independent and -dependent manner, respectively

The nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma) activates the transcription of multiple genes involved in intra- and extracellular lipid metabolism. Several cofactors are crucial for the stimulation or the silencing of nuclear receptor transcriptional activities. The two homologous cofactors p300 and CREB-binding protein (CBP) have been shown to co-activate the ligand-dependent transcriptional activities of several nuclear receptors as well as the ligand-independent transcriptional activity of the androgen receptor. We show here that the interaction between p300/CBP and PPAR gamma is complex and involves multiple domains in each protein, p300/CBP not only bind in a ligand-dependent manner to the DEF region of PPAR gamma but also bind directly in a ligand-independent manner to a region in the AB domain localized between residue 31 to 99, In transfection experiments, p300/CBP could thereby enhance the transcriptional activities of both the activating function (AF)-1 and AF-2 domains. p300/CBP displays itself at least two docking sites for PPAR gamma located in its N terminus (between residues 1 and 113 for CBP) and in the middle of the protein (between residues 1099 and 1460).