PGC-1 alpha co-activates transcription by several nuclear receptors. To study the interaction among PGC-1 alpha, RXR alpha/FXR, and DNA, We performed electrophoresis mobility shift assays. The RXR alpha/FXR proteins specifically bound to DNA containing the IR-1 sequence in the absence of ligand. When the fusion protein of GST-PGC-1 alpha was added to the mixture of RXR alpha/FXR/DNA, the ligand-influenced retardation of the mobility was observed. The ligand for RXR alpha (9-cis-retinoic acid) was necessary for this retardation, whereas, the ligand for FXR, chenodeoxycholic acid, barely had an effect. The results obtained using truncated PGC-1 alpha proteins suggested that two regions are necessary for PGC-1 alpha to interact with the DNA-binding complex of RXR alpha/FXR. One is the region of the second leucine-rich motif, and the other is that of the amino acid sequence CQQQKPQRRP, present between the second and third leucine-rich motifs. The results obtained with the SPQSS Mutation for KPQRR suggested that the basic amino acids are important for the interaction. (c) 2006 Elsevier Inc. All rights reserved.