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Stimulus-dependent differential regulation in the Escherichia coli PhoQ-PhoP system

机译:大肠杆菌PhoQ-PhoP系统中依赖刺激的差异调节

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摘要

In Escherichia coli, Salmonella, and related bacteria, the PhoQ-PhoP system regulates the expression of a large collection of genes in response to conditions of low magnesium or to the presence of certain antimicrobial peptides. We measured transcription of four PhoP-regulated promoters in E. coli that have significantly different PhoP-binding sites. Surprisingly, three promoters show identical responses to magnesium concentrations that range over four orders of magnitude. By analyzing and testing a simple model of transcriptional regulation, we find an explanation for this puzzle and show that these promoters are indeed differentially regulated at sufficiently high levels of stimulus. We then use this analysis to infer an effective level of phosphorylated PhoP as a function of magnesium stimulus. Our results demonstrate that differential regulation generally depends on the strength of the stimulus and highlight how quantitative analysis of stimulus-response curves can be used to infer properties of cell regulatory circuits that cannot be easily obtained from in vitro measurements.
机译:在大肠杆菌,沙门氏菌和相关细菌中,PhoQ-PhoP系统响应低镁条件或某些抗菌肽的存在而调节大量基因的表达。我们测量了在大肠杆菌中具有明显不同的PhoP结合位点的四个PhoP调节启动子的转录。令人惊讶地,三个启动子对镁浓度范围超过四个数量级的反应显示相同。通过分析和测试一个简单的转录调控模型,我们找到了这个难题的解释,并表明这些启动子的确在足够高的刺激水平下受到了不同的调控。然后,我们使用此分析推断出磷酸化PhoP的有效水平与镁刺激的关系。我们的结果表明,差异调节通常取决于刺激的强度,并强调了如何将刺激-反应曲线的定量分析用于推断细胞调节电路的特性,而这些特性在体外测量中不易获得。

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