基于 Hill 函数的转录响应模型：非特异性结合与 RNAP 相互作用的影响
Hill Function-based Model of Transcriptional Response: Impact of Nonspecific Binding and RNAP Interactions
AI总结：
该研究从 TF、RNAP 与 DNA 特异性及非特异性位点的反应出发推导转录倍数变化，阐明弱启动子下其与 Hill 函数的联系及参数生化含义。
摘要：
Hill 函数是被广泛使用的基因转录调控模型之一。其拟合属性可能导致缺乏底层物理图像，但拟合参数能够提供有关生化反应的信息，例如转录因子（TF）的数量以及调控元件之间的结合能。然而，目前仍不清楚 Hill 函数除拟合之外何时能够提供多少生化信息。本文从转录调控过程中 TF 与 RNA 聚合酶之间的相互作用，以及二者在 DNA 上特异性/非特异性位点处的结合—解离反应出发，将 TF 的调控效应推导为倍数变化。研究发现，对于弱启动子，倍数变化可退化为与 Hill 函数密切相关的调控因子（Freg）。通过与 Hill 函数直接比较和拟合，分析并讨论了 Freg 中的拟合参数及相应的生化反应参数，其中考虑了单个 TF 以及具有协同性和基本逻辑效应的多个 TF。本文得出结论：启动子强度和 TF 之间的相互作用决定 Hill 函数能否反映相应的生化信息。这些发现强调了 Hill 函数在转录调控建模/拟合中的作用，也有利于合成调控元件的制备。
英文摘要：
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.
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