Activity of the pleiotropic drug resistance transcription factors Pdr1p and Pdr3p is modulated by binding site flanking sequences

The transcription factors Pdr1p and Pdr3p regulate pleiotropic drug resistance (PDR) in Saccharomyces cerevisiae via the PDR responsive elements (PDREs) to modulate gene expression. However, the exact mechanisms underlying the differences in their regulons remain unclear. Employing genomic occupancy profiling (CUT&RUN), binding assays, and transcription studies, we characterized the differences in sequence specificity between transcription factors. Findings reveal distinct preferences for core PDRE sequences and the flanking sequences for both proteins. While flanking sequences moderately alter DNA binding affinity, they significantly impact Pdr1/3p transcriptional activity. Notably, both proteins demonstrated the ability to bind half sites, showing potential enhancement of transcription from adjacent PDREs. This insight sheds light on ways Pdr1/3p can differentially regulate PDR.