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

The PDR network is an important regulatory system in yeast involved in the transport of various toxins and drugs out of the cell. The transcription factors Pdr1p and Pdr3p, key regulators of this network, bind to specific sequences called PDREs in the promoter region of PDR genes to control expression. However, the exact mechanism underlying the differences in the regulons of these proteins are not well understood. A combination of genomic occupancy profiling (CUT&RUN) and in vitro binding assays were employed to characterize the differences in sequence specificity between transcription factors. The results indicate that interaction between the transcription factors and PDRE sites is not solely determined by the core sequence, but also influenced by the surrounding regions.PDR网络（PDR network）是酵母中一类重要的调控系统，负责将多种毒素与药物转运出细胞。作为该网络的核心调控因子，转录因子Pdr1p与Pdr3p可结合PDR基因启动子区域内名为PDRE（PDRE）的特定序列，以此调控基因表达。然而，目前对于这两种调控蛋白的调控子（regulons）之间差异的确切分子机制仍未被充分阐明。本研究结合基因组占位谱分析（CUT&RUN）与体外结合实验，对这两种转录因子的序列结合特异性差异展开了表征。研究结果表明，转录因子与PDRE位点的相互作用并非仅由核心序列决定，同时还会受到其侧翼序列区域的影响。