Positive autoregulation shapes response timing and intensity in two-component signal transduction systems.
Positive autoregulation shapes response timing and intensity in two-component signal transduction systems.
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DOI：
10.1016/j.jmb.2010.06.051
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发表时间：
2010-08-27
影响因子：
5.6
通讯作者：
Groisman EA
中科院分区：
文献类型：
--
作者：
Mitrophanov AY;Hadley TJ;Groisman EA
正反馈环是调控基因表达输出、动力学和噪声的调控元件。参与这种环的转录调节因子通常由两个启动子表达-一个组成型启动子和一个自调节启动子。在这里，我们调查的相互作用的启动子强度和强度的刺激激活转录调节因子在定义一个积极的自我调节的遗传电路的输出。使用一个数学模型的两个组件的监管系统，这是目前在生活的各个领域，我们建立了正反馈强烈影响稳态输出水平在低和高的刺激，如果调节器的组成型启动子是弱的。相比之下，当组成型启动子足够强时，正反馈的效果可以忽略不计，除非刺激强度非常高。此外，我们确定，即使在最简单的基因调控系统中，正反馈也会影响瞬态和稳态输出水平。我们通过废除肠道沙门氏菌双组分调控系统PhoP/PhoQ中的正反馈回路来测试我们的建模预测，这导致PhoP激活基因的诱导减少。
Positive feedback loops are regulatory elements that can modulate expression output, kinetics and noise in genetic circuits. Transcriptional regulators participating in such loops are often expressed from two promoters – one constitutive and one autoregulated. Here we investigate the interplay of promoter strengths and the intensity of the stimulus activating the transcriptional regulator in defining the output of a positively autoregulated genetic circuit. Using a mathematical model of two-component regulatory systems, which are present in all domains of life, we establish that positive feedback strongly affects the steady-state output levels at both low and high stimulus if the regulator’s constitutive promoter is weak. By contrast, the effect of positive feedback is negligible when the constitutive promoter is sufficiently strong, unless the stimulus intensity is very high. Furthermore, we determine that positive feedback can affect both transient and steady-state output levels even in the simplest genetic regulatory systems. We tested our modeling predictions by abolishing the positive feedback loop in the two-component regulatory system PhoP/PhoQ of Salmonella enterica, which resulted in diminished induction of PhoP-activated genes.
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影响因子：
--
作者：
Kaznessis, Yiannis N.
通讯作者：
Kaznessis, Yiannis N.
影响因子：
3.2
作者：
Lejona, S;Castelli, ME;Soncini, FC
通讯作者：
Soncini, FC
DOI：
10.1126/science.1160617
发表时间：
2008-10-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Brandman O;Meyer T
通讯作者：
Meyer T
影响因子：
5.4
作者：
Goulian, Mark
通讯作者：
Goulian, Mark
控制肠细菌中多粘质B抗性的调节结构的进化和动力学。
影响因子：
4.5
作者：
Mitrophanov, Alexander Y.;Jewett, Mollie W.;Hadley, Tricia J.;Groisman, Eduardo A.
通讯作者：
Groisman, Eduardo A.