Analytical distribution and tunability of noise in a model of promoter progress.
Analytical distribution and tunability of noise in a model of promoter progress.
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DOI：
10.1016/j.bpj.2012.02.001
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发表时间：
2012-03
影响因子：
3.4
通讯作者：
Jiajun Zhang;Luonan Chen;Tianshou Zhou
中科院分区：
文献类型：
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作者：
Jiajun Zhang;Luonan Chen;Tianshou Zhou
染色质模板（CT），随着时间的推移积累，直到启动子变得活跃，决定转录的上游动力学，但上游顺序步骤如何影响下游动力学定性和定量尚不清楚。在这里，我们分析了一个随机基因模型与一个简单而典型的CT，包含一个活跃的状态和几个非活跃状态的启动子。我们推导出的解析表达式的mRNA概率分布的噪声由主方程。衍生的结果扩展了以前的工作，包括变异性和双峰启动子的进展的影响。具体而言，给定一个CT的转录，我们分析表明，启动子的非活性阶段可以调节噪声强度的最小独立的mRNA的平均表达。如果一个新的非活动状态被添加到CT，则所产生的噪声将被降低，这意味着多关断机制起到衰减噪声的作用。与简单的开-关机制相比，多关机制还可以在某个参数平面上缩小双峰区域并掩盖两个峰，这解释了为什么在实验中很少观察到双峰分布。我们的研究结果提供了深入了解的作用，启动子的进展，在决定水平的细胞间的变异基因表达。
Chromatin template (CT), which accumulates over time until the promoter becomes active, determines upstream dynamics of transcription, but how upstream sequential steps impact downstream dynamics qualitatively and quantitatively is unclear. Here, we analyze a stochastic gene model with a simple yet typical CT that contains one active state and several inactive states of the promoter. We derive the analytical expressions for the noise in mRNA probability distributions governed by master equations. The derived results extend previous work by including the effects of promoter progress on variability and bimodality. Specifically, given a CT for transcription, we analytically demonstrate that inactive phases of the promoter can modulate the noise intensity to the minimum independently of the mean expression of mRNA. If one new inactive state is added to the CT, then the resulting noise will be reduced, implying that the multi-off mechanism plays a role of attenuating the noise. In contrast to the simple on-off mechanism, the multi-off mechanism can also narrow bimodal regions in a certain parameter plane and obscure two peaks, explaining why bimodal distributions are rarely observed in experiments. Our results provide insight into the role of promoter progress in determining the level of cell-to-cell variability in gene expression.