Ordering up gene expression by slowing down transcription factor binding kinetics.

Ordering up gene expression by slowing down transcription factor binding kinetics.
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DOI:
10.1007/s00294-018-0896-7
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发表时间:
2019-04
期刊:
影响因子:
2.5
通讯作者:
Culyba MJ
Culyba MJ
中科院分区:
生物学3区
文献类型:
--
作者:
Culyba MJ

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复杂遗传反应的有效调控要求催化反应的基因产物以时间有序的方式合成,以匹配它们作用的反应途径的顺序性质。转录调节网络通过随时间调节转录因子(TF)浓度来协调细胞控制的这一方面。TF对基因表达时间的影响通常是假设TF-启动子结合反应与TF浓度随时间的变化处于热力学平衡,然而,相对缓慢的TF结合动力学导致的非平衡动力学可能导致不同的网络行为。在这里,我强调了最近的细菌SOS反应,其中一个单一的TF调节多个目标启动子的研究,以显示如何在一个更复杂的行为,使启动子的活动,不仅取决于缓慢的TF结合动力学在启动子的时间间隔更大的TF结合不平衡的结果,但也对响应刺激的大小。我还讨论了依赖特定的TF调节机制和影响网络行为的非平衡动力学的随机基因表达。
Efficient regulation of a complex genetic response requires that the gene products, which catalyze the response, be synthesized in a temporally ordered manner to match the sequential nature of the reaction pathway they act upon. Transcription regulation networks coordinate this aspect of cellular control by modulating transcription factor (TF) concentrations through time. The effect a TF has on the timing of gene expression is often modeled assuming that the TF-promoter binding reaction is in thermodynamic equilibrium with changes in TF concentration over time, however, non-equilibrium dynamics resulting from relatively slow TF binding kinetics can result in different network behavior. Here, I highlight a recent study of the bacterial SOS response, where a single TF regulates multiple target promoters, to show how a disequilibrium of TF binding at promoters results in a more complex behavior, enabling a larger temporal separation of promoter activities that depends not only upon slow TF binding kinetics at promoters, but also on the magnitude of the response stimulus. I also discuss the dependence of network behavior on specific TF regulatory mechanisms and the implications non-equilibrium dynamics have for stochastic gene expression.
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