DNA binding preferences of PPAR alpha/RXR alpha heterodimers

The regulatory elements mediating the transcriptional effects of the Peroxisome Proliferator Activated Receptor (PPAR)/Retinoid X Receptor heterodimers consist of a direct repeat of a variant of the consensus hexamer AGGTCA with an interspacing of 1 basepair (DR1). A binding site selection was performed to investigate whether any further constraints for PPAR/RXR binding to DR1 elements exist and/or whether other high affinity binding sites for these heterodimers can be identified. One half of the recovered sequences contained two hexamers related to the consensus halfsite organised as DR1, DR2, PAL0 or as DR3, in diminishing order of frequency. The other binding sites consisted of three hexamer repeats with the number of interspacing bases varying between 0 and 7. An element with three consecutive hexamer sequences each spaced by 1 basepair was most efficient in mediating the effects of peroxisome proliferators. The results indicate that the upstream flanking sequence of a DR1 differentially influences the binding of PPAR alpha/RXR alpha heterodimers and of RXR alpha homodimers.