THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR INTERACTS WITH THE RETINOID-X RECEPTOR IN-VIVO

The peroxisome proliferator-activated receptor (PPAR) binds cooperativ ely to cognate peroxisome proliferator-responsive elements (PPRE) in v itro through heterodimerization with retinoid X receptors (RXR). We us ed the yeast two-hybrid system to determine whether these two nuclear receptors physically interact in vivo. Mouse (m) PPAR and human (h) RX R alpha were synthesized as fusion proteins to either the DNA-binding domain (GBD) or the transactivation domain (GAD) of the yeast GAL4 tra nscription-activator protein, and were tested for their ability to act ivate expression of a GAL1::lacZ reporter gene. Strong activation was observed only in yeast transformed with combinations of GBD::mPPAR and GAD::hRXR alpha or with GAD::mPPAR and GBD::hRXR alpha. Homodimeric i nteraction by mPPAR was not detected. These results provide evidence f or the interaction of PPAR and RXR alpha in vivo in the absence of a P PRE target site or exogenously added ligands.