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Anticipating response function in gene regulatory networks
Journal of The Royal Society Interface ( IF 3.7 ) Pub Date : 2021-06-02 , DOI: 10.1098/rsif.2021.0206
Pankaj Gautam 1 , Sudipta Kumar Sinha 1
Affiliation  

The origin of an ordered genetic response of a complex and noisy biological cell is intimately related to the detailed mechanism of protein–DNA interactions present in a wide variety of gene regulatory (GR) systems. However, the quantitative prediction of genetic response and the correlation between the mechanism and the response curve is poorly understood. Here, we report in silico binding studies of GR systems to show that the transcription factor (TF) binds to multiple DNA sites with high cooperativity spreads from specific binding sites into adjacent non-specific DNA and bends the DNA. Our analysis is not limited only to the isolated model system but also can be applied to a system containing multiple interacting genes. The controlling role of TF oligomerization, TF–ligand interactions, and DNA looping for gene expression has been also characterized. The predictions are validated against detailed grand canonical Monte Carlo simulations and published data for the lac operon system. Overall, our study reveals that the expression of target genes can be quantitatively controlled by modulating TF–ligand interactions and the bending energy of DNA.



中文翻译:

预测基因调控网络中的反应功能

复杂而嘈杂的生物细胞的有序遗传反应的起源与存在于各种基因调控 (GR) 系统中的蛋白质-DNA 相互作用的详细机制密切相关。然而,人们对遗传反应的定量预测以及机制与反应曲线之间的相关性知之甚少。在这里,我们在 silico报告GR系统的结合研究表明转录因子(TF)以高协同性与多个DNA位点结合,从特异性结合位点扩散到相邻的非特异性DNA并弯曲DNA。我们的分析不仅限于孤立的模型系统,还可以应用于包含多个相互作用基因的系统。TF 寡聚化、TF-配体相互作用和 DNA 环化对基因表达的控制作用也得到了表征。这些预测根据详细的大规范蒙特卡罗模拟和lac操纵子系统的已发布数据进行了验证。总体而言,我们的研究表明,可以通过调节 TF-配体相互作用和 DNA 的弯曲能量来定量控制靶基因的表达。

更新日期:2021-06-02
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