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A Nonlinear Discrete Dynamical Model for Transcriptional Regulation: Construction and Properties

机译:转录调控的非线性离散动力学模型:构造和性质

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摘要

Transcriptional regulation is a fundamental mechanism of living cells, which allows them to determine their actions and properties, by selectively choosing which proteins to express and by dynamically controlling the amounts of those proteins. In this article, we revisit the problem of mathematically modeling transcriptional regulation. First, we adopt a biologically motivated continuous model for gene transcription and mRNA translation, based on first-order rate equations, coupled with a set of nonlinear equations that model cis-regulation. Then, we view the processes of transcription and translation as being discrete, which, together with the need to use computational techniques for large-scale analysis and simulation, motivates us to model transcriptional regulation by means of a nonlinear discrete dynamical system. Classical arguments from chemical kinetics allow us to specify the nonlinearities underlying cis-regulation and to include both activators and repressors as well as the notion of regulatory modules in our formulation. We show that the steady-state behavior of the proposed discrete dynamical system is identical to that of the continuous model. We discuss several aspects of our model, related to homeostatic and epigenetic regulation as well as to Boolean networks, and elaborate on their significance. Simulations of transcriptional regulation of a hypothetical metabolic pathway illustrate several properties of our model, and demonstrate that a nonlinear discrete dynamical system may be effectively used to model transcriptional regulation in a biologically relevant way.
机译:转录调控是活细胞的基本机制,通过选择性地选择表达哪些蛋白质并动态控制这些蛋白质的数量,可以使它们确定其作用和特性。在本文中,我们将重新探讨对转录调控进行数学建模的问题。首先,我们基于一级速率方程,结合一套以顺式调控为模型的非线性方程,采用生物学动机连续的基因转录和mRNA翻译模型。然后,我们认为转录和翻译的过程是离散的,再加上需要将计算技术用于大规模分析和模拟,这促使我们通过非线性离散动力系统对转录调控进行建模。化学动力学的经典论据使我们能够指定顺式调节的非线性因素,并在我们的配方中包括活化剂和阻遏剂以及调节模块的概念。我们表明,所提出的离散动力系统的稳态行为与连续模型的稳态行为相同。我们讨论了与稳态和表观遗传调控以及布尔网络有关的模型的几个方面,并详细说明了它们的重要性。假设的代谢途径的转录调控的模拟说明了我们模型的几个特性,并证明了非线性离散动力系统可以有效地以生物学相关的方式对转录调控进行建模。

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