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Stochastic Stabilization of Phenotypic States: The Genetic Bistable Switch as a Case Study

机译:表型状态的随机稳定:遗传双稳态开关作为一个案例研究

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摘要

We study by means of analytical calculation and stochastic simulations how intrinsic noise modifies the bifurcation diagram of gene regulatory processes that can be effectively described by the Langevin formalism. In a general context, our study raises the intriguing question of how biochemical fluctuations redesign the epigenetic landscape in differentiation processes. We have applied our findings to a general class of regulatory processes that includes the simplest case that displays a bistable behavior and hence phenotypic variability: the genetic auto-activating switch. Thus, we explain why and how the noise promotes the stability of the low-state phenotype of the switch and show that the bistable region is extended when increasing the intensity of the fluctuations. This phenomenology is found in a simple one-dimensional model of the genetic switch as well as in a more detailed model that takes into account the binding of the protein to the promoter region. Altogether, we prescribe the analytical means to understand and quantify the noise-induced modifications of the bifurcation points for a general class of regulatory processes where the genetic bistable switch is included.
机译:我们通过分析计算和随机模拟的方法研究内在噪声如何修改基因调控过程的分叉图,这可以由Langevin形式主义有效地描述。在一般情况下,我们的研究提出了一个有趣的问题,即生化波动如何在分化过程中重新设计表观遗传景观。我们已将研究结果应用于一类常规的监管程序,其中包括显示双稳态行为并因此表现出表型变异的最简单情况:遗传自动激活开关。因此,我们解释了噪声为什么以及如何促进开关的低态表型的稳定性,并表明当增加波动强度时,双稳态区域会扩展。这种现象学是在遗传转换的简单一维模型以及考虑到蛋白质与启动子区域结合的更详细模型中发现的。总的来说,我们规定了一种分析手段,以理解和量化噪声引起的分叉点对一般类别的调节过程的分叉点的修饰,其中遗传双稳态开关被包括在内。

著录项

  • 期刊名称 other
  • 作者

    Marc Weber; Javier Buceta;

  • 作者单位
  • 年(卷),期 -1(8),9
  • 年度 -1
  • 页码 e73487
  • 总页数 8
  • 原文格式 PDF
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