Hill Function-based Model of Transcriptional Response: Impact of Nonspecific Binding and RNAP Interactions

Wenjia Shi, Yao Ma, Peilin Hu, Mi Pang, Xiaona Huang, Yiting Dang, Yuxin Xie, Danni Wu
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Abstract

Hill function is one of the widely used gene transcription regulation models. Its attribute of fitting may result in a lack of an underlying physical picture, yet the fitting parameters can provide information about biochemical reactions, such as the number of transcription factors (TFs) and the binding energy between regulatory elements. However, it remains unclear when and how much biochemical information can Hill function provide in addition to fitting. Here, started from the interactions between TFs and RNA polymerase during transcription regulation and both of their association-dissociation reactions at specific/nonspecific sites on DNA, the regulatory effect of TFs was deduced as fold change. We found that, for weak promoter, fold change can degrade into the regulatory factor (Freg) which is closely correlated with Hill function. By directly comparing and fitting with Hill function, the fitting parameters and corresponding biochemical reaction parameters in Freg were analyzed and discussed, where the single TF and multiple TFs that with cooperativity and basic logic effects were considered. We concluded the strength of promoter and interactions between TFs determine whether Hill function can reflect the corresponding biochemical information. Our findings highlight the role of Hill function in modeling/fitting for transcriptional regulation, which also benefits the preparation of synthetic regulatory elements.
基于希尔功能的转录反应模型:非特异性结合和 RNAP 相互作用的影响
希尔函数是被广泛使用的基因转录调控模型之一。它的拟合属性可能导致缺乏基本的物理图像,但拟合参数可以提供生化反应信息,如转录因子(TFs)的数量和调控元件之间的结合能。在此,我们从转录调控过程中 TFs 与 RNA 聚合酶之间的相互作用以及它们在 DNA 上特异/非特异位点的结合-解离反应入手,推导出 TFs 的调控效应折叠变化。我们发现,对于弱启动子,折叠变化可降解为与希尔函数密切相关的调控因子(Freg)。通过与希尔函数的直接比较和拟合,分析和讨论了 Freg 中的拟合参数和相应的生化反应参数,其中考虑了单个 TF 和具有合作性和基本逻辑效应的多个 TF。我们的结论是,启动子的强度和 TF 之间的相互作用决定了希尔函数能否反映相应的生化信息。我们的研究结果突出了希尔函数在转录调控建模/拟合中的作用,这也有利于合成调控元件的制备。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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