摘要

压力反应网络通常有一个上游调控因子控制许多下游基因。然而，下游目标通常是多种多样的，因此，在共同监管机构的指导下，它们的表达如何专门化仍不清楚。为了解决这个问题，我们专注于应激反应网络，其中来自大肠杆菌的多种抗生素抗性激活剂MarA调节从小RNA到外排泵的多种靶标。使用单细胞实验和计算模型，我们发现所研究的每个下游基因具有不同的活化，噪音和信息传递特性。重要的是，我们的结果表明了解生物环境是至关重要的;我们发现这样的例子，其中强激活仅发生在MarA的生理相关范围之外，而其他的野生型MarA水平的噪声较高并且随着MarA达到其生理极限而降低。这些结果表明单个调控蛋白如何在保持特异性的同时协调许多下游基因的反应。

Stress response networks frequently have a single upstream regulator that controls many downstream genes. However, the downstream targets are often diverse, therefore it remains unclear how their expression is specialized when under the command of a common regulator. To address this, we focused on a stress response network where the multiple antibiotic resistance activator MarA from Escherichia coli regulates diverse targets ranging from small RNAs to efflux pumps. Using single-cell experiments and computational modeling, we showed that each downstream gene studied has distinct activation, noise, and information transmission properties. Critically, our results demonstrate that understanding biological context is essential; we found examples where strong activation only occurs outside physiologically relevant ranges of MarA and others where noise is high at wild type MarA levels and decreases as MarA reaches its physiological limit. These results demonstrate how a single regulatory protein can maintain specificity while orchestrating the response of many downstream genes.

http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005310&rev=1