Dissecting specific and global transcriptional regulation of bacterial gene expression
Dissecting specific and global transcriptional regulation of bacterial gene expression
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DOI：
10.1038/msb.2013.14
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发表时间：
2013-04-01
影响因子：
9.9
通讯作者：
Sauer, Uwe
中科院分区：
文献类型：
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作者：
Gerosa, Luca;Kochanowski, Karl;Sauer, Uwe
基因表达受特定转录回路的调节，但也受作为生长功能的全局表达机制的调节。因此，同时进行的特异性和全局调控构成了基因表达中额外但经常被忽视的复杂性层。在这里，我们开发了一种实验计算方法来剖析大肠杆菌的特定和全局调节。通过使用荧光启动子记者，我们表明全局调节不仅在稳态期间而且在生长速率的动态变化期间都依赖于生长速率，并且可以通过两个启动子特异性参数来量化。通过应用我们的精氨酸生物合成方法，我们获得了对特定和全局调节的定量了解，从而可以准确预测对精氨酸可用性和生长率同时扰动的时间响应。因此，我们揭示了联合调控的两个原则：（i）通过抑制进行的特异性调控主导了代谢稳态期间的转录反应，即使需要生物合成，也很大程度上抑制了生物合成基因；（ii）全局调控设定了稳态之间过渡期间利用的最大启动子活性。
Gene expression is regulated by specific transcriptional circuits but also by the global expression machinery as a function of growth. Simultaneous specific and global regulation thus constitutes an additional-but often neglected-layer of complexity in gene expression. Here, we develop an experimental-computational approach to dissect specific and global regulation in the bacterium Escherichia coli. By using fluorescent promoter reporters, we show that global regulation is growth rate dependent not only during steady state but also during dynamic changes in growth rate and can be quantified through two promoter-specific parameters. By applying our approach to arginine biosynthesis, we obtain a quantitative understanding of both specific and global regulation that allows accurate prediction of the temporal response to simultaneous perturbations in arginine availability and growth rate. We thereby uncover two principles of joint regulation: (i) specific regulation by repression dominates the transcriptional response during metabolic steady states, largely repressing the biosynthesis genes even when biosynthesis is required and (ii) global regulation sets the maximum promoter activity that is exploited during the transition between steady states.