Jiao Feng, Zhu Chunjuan
Center for Applied Mathematics, Guangzhou University, Guangzhou, P. R. China; College of Mathematics and Information Sciences, Guangzhou University, Guangzhou, P.R. China.
Modern Business and Management Department, Guangdong Construction Polytechnic, Guangzhou, P. R. China; College of Mathematics and Information Sciences, Guangzhou University, Guangzhou, P.R. China.
Biophys J. 2020 Sep 15;119(6):1204-1214. doi: 10.1016/j.bpj.2020.08.011. Epub 2020 Aug 19.
The phenomenon of a gene expression burst has been attributed to random transitions between the active and inactive states of a gene. However, the mechanisms underlying regulation of the activation process in response to environmental changes remain unclear. Here, we model gene activation as a consequence of the competitive cross talk between a weak basal pathway and an inducible signaling pathway and reveal rich expression dynamics along with intricate dependence of noise and Fano factor on mean expression levels. These theoretical results are in good agreement with a large experimental data set in Escherichia coli, yeast, and mammalian cells. Furthermore, both theoretical analyses and supporting biological evidence converge to demonstrate the existence of a tradeoff that governs the sharp up- and downregulation of gene expression, suggesting an ordered scenario that activates a gene under varying conditions. These regulation modes, together with cross talk pathways, may provide new guidance for the analysis and interpretation of genetic data in various applications, ranging from genetic engineering to therapeutic targets of disease.
基因表达爆发现象被认为是基因在活跃和非活跃状态之间随机转换的结果。然而，响应环境变化时激活过程的调控机制仍不清楚。在这里，我们将基因激活建模为弱基础途径和诱导信号途径之间竞争性相互作用的结果，并揭示了丰富的表达动态以及噪声和Fano因子对平均表达水平的复杂依赖性。这些理论结果与大肠杆菌、酵母和哺乳动物细胞中的大量实验数据集高度吻合。此外，理论分析和支持性生物学证据都表明存在一种权衡，它控制着基因表达的急剧上调和下调，这表明在不同条件下激活基因存在一种有序的情况。这些调控模式以及相互作用途径，可能为各种应用中的遗传数据分析和解释提供新的指导，从基因工程到疾病治疗靶点。
