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Regulation of gene activation by competitive cross-talking pathways
Biophysical Journal ( IF 3.4 ) Pub Date : 2020-09-01 , DOI: 10.1016/j.bpj.2020.08.011
Feng Jiao 1 , Chunjuan Zhu 2
Affiliation  

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.

中文翻译:

竞争性串扰通路调控基因激活

基因表达爆发的现象归因于基因的活跃和非活跃状态之间的随机转换。然而,响应环境变化的激活过程的调节机制仍不清楚。在这里,我们将基因激活建模为弱基础通路和诱导信号通路之间竞争性串扰的结果,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型实验数据集非常吻合。此外,理论分析和支持的生物学证据都表明存在控制基因表达急剧上调和下调的权衡,暗示在不同条件下激活基因的有序场景。这些调控模式,连同串扰通路,可以为从基因工程到疾病治疗靶点的各种应用中的基因数据的分析和解释提供新的指导。
更新日期:2020-09-01
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