Computer Simulation and Modelling (Co.S.Mo.) Lab, Parc Científic de Barcelona, Barcelona, Spain.
PLoS One. 2013 Sep 11;8(9):e73487. doi: 10.1371/journal.pone.0073487. eCollection 2013.
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.
我们通过分析计算和随机模拟研究了内禀噪声如何改变可以用 Langevin 公式有效描述的基因调控过程的分岔图。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。我们将我们的发现应用于一类包括最简单的显示双稳态行为和因此表型可变性的调节过程：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状态表型的稳定性，并表明当增加波动强度时，双稳态区域会扩展。这种现象学在遗传开关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都有发现。总的来说，我们规定了分析手段来理解和量化一类调节过程中分叉点的噪声诱导变化，其中包括遗传双稳态开关。
