一个多ON基因系统的表达动力学分析

The Analysis of Expression Dynamics in a Multi-On Gene System

研究了一个转录水平上的基因表达模型,它不仅考虑了启动子的复杂性,而且考虑了相互作用转录因子的调控效果.假定启动子区域有2个调控位点,启动子有1个失活态和2个激活态(即2个不同的转录出口),并考虑了绑定到不同调控位点的转录因子之间相互作用的3种代表性机制:招募机制,稳定机制和混合机制.理论分析和数值模拟结果显示:不同的转录出口能够导致m RNA分布峰的多样性;3种机制下的平均表达水平和平均爆发频率都相同,但稳定机制诱导最大的表达噪声和平均爆发规模,而招募机制诱导最小的表达噪声和平均爆发规模.这些结果表明:细胞表型的产生源是复杂的,既与启动子结构有关也与调控机制有关.

The relationship between cellular phenotype across a genetically identical population and gene expression difference has being a very active topic. Here,a gene expression model at the transcription level is studied,considering not only complexity of promoter structure but also interactive effect between transcription factors. The promoter region is assumed to contain two regulatory sites and the promoter has one inactive state and two active states（ i.e.,two different transcription exits）. In addition,based on interaction between transcription factors binding to the different regulatory sites,three representative mechanisms are considered,including recruitment mechanism,stabilization mechanism and mixture mechanism. Theoretical analysis and numerical simulation results show that different transcription exits can lead to m RNA distribution peaks of different modes; the m RNA mean level and mean burst frequency are identical under these three mechanisms,but stabilization mechanism induces the highest expression noise and the largest mean burst size,and recruitment mechanism induces the lowest expression noise and the smallest mean burst size. These results indicate that the source of cellular phenotype is complex,which is related to both promoter structure and regulation mechanisms.