Stimulus-dependent differential regulation in the Escherichia coli PhoQ-PhoP system
Stimulus-dependent differential regulation in the Escherichia coli PhoQ-PhoP system
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DOI：
10.1073/pnas.0700025104
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发表时间：
2007-10-09
影响因子：
11.1
通讯作者：
Goulian, Mark
中科院分区：
文献类型：
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作者：
Miyashiro, Tim;Goulian, Mark
在大肠杆菌、沙门氏菌和相关细菌中，PhoQ-PhoP系统调节大量基因的表达，以响应低镁条件或某些抗菌肽的存在。我们在大肠杆菌中测定了四个PhoP调控的启动子的转录。具有显著不同的PhoP结合位点的大肠杆菌。令人惊讶的是，三个启动子显示出相同的反应范围超过四个数量级的镁浓度。通过分析和测试一个简单的模型的转录调控，我们找到了这个难题的解释，并表明，这些启动子确实差异调节足够高的刺激水平。然后，我们使用这种分析来推断磷酸化PhoP的有效水平作为镁刺激的函数。我们的研究结果表明，差分调节一般取决于刺激的强度，并强调如何刺激-响应曲线的定量分析可以用来推断不能很容易地从体外测量获得的细胞调节电路的属性。
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.