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首页> 外文期刊>Molecular and Cellular Biology >New Insights into the Pleiotropic Drug Resistance Network from Genome-Wide Characterization of the YRR1 Transcription Factor Regulation System
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New Insights into the Pleiotropic Drug Resistance Network from Genome-Wide Characterization of the YRR1 Transcription Factor Regulation System

机译：YRR1转录因子调控系统的全基因组表征对多效耐药性网络的新见解

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摘要

Yrr1p is a recently described Zn2Cys6 transcription factor involved in the pleiotropic drug resistance (PDR) phenomenon. It is controlled in a Pdr1p-dependent manner and is autoregulated. We describe here a new genome-wide approach to characterization of the set of genes directly regulated by Yrr1p. We found that the time-course production of an artificial chimera protein containing the DNA-binding domain of Yrr1p activated the 15 genes that are also up-regulated by a gain-of-function mutant of Yrr1p. Gel mobility shift assays showed that the promoters of the genes AZR1, FLR1, SNG1, YLL056C, YLR346C, and YPL088W interacted with Yrr1p. The putative consensus Yrr1p binding site deduced from these experiments, (T/A)CCG(C/T)(G/T)(G/T)(A/T)(A/T), is strikingly similar to the PDR element binding site sequence recognized by Pdr1p and Pdr3p. The minor differences between these sequences are consistent with Yrr1p and Pdr1p and Pdr3p having different sets of target genes. According to these data, some target genes are directly regulated by Pdr1p and Pdr3p or by Yrr1p, whereas some genes are indirectly regulated by the activation of Yrr1p. Some genes, such as YOR1, SNQ2, and FLR1, are clearly directly controlled by both classes of transcription factor, suggesting an important role for the corresponding membrane proteins.
机译：Yrr1p是最近描述的涉及多效药物耐药性（PDR）现象的Zn 2 Cys 6 转录因子。它以Pdr1p依赖的方式进行控制并且是自动调节的。我们在这里描述了一种新的全基因组方法来表征由Yrr1p直接调控的一组基因。我们发现时程产生的人工嵌合蛋白包含Yrr1p的DNA结合域激活了15个基因，这些基因也被Yrr1p的功能获得突变体上调。凝胶迁移率迁移分析显示 AZR1 ， FLR1 ， SNG1 ， YLL056C ， YLR346C 和 YPL088W 与Yrr1p进行了交互。从这些实验推导出的推定共有Yrr1p结合位点（T / A）CCG（C / T）（G / T）（G / T）（A / T）（A / T）与PDR元素极为相似Pdr1p和Pdr3p识别的结合位点序列。这些序列之间的微小差异与具有不同靶基因组的Yrr1p和Pdr1p和Pdr3p一致。根据这些数据，某些靶基因直接受Pdr1p和Pdr3p或Yrr1p调控，而某些基因则受Yrr1p激活间接调控。显然，某些基因（例如 YOR1 ， SNQ2 和 FLR1 ）直接受这两类转录因子的控制，这提示它们对相应的膜蛋白。

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