RESUMO
The ability of living cells to maintain an inheritable memory of their gene-expression state is key to cellular differentiation. Bacterial lysogeny serves as a simple paradigm for long-term cellular memory. In this study, we address the following question: in the absence of external perturbation, how long will a cell stay in the lysogenic state before spontaneously switching away from that state? We show by direct measurement that lysogen stability exhibits a simple exponential dependence on the frequency of activity bursts from the fate-determining gene, cI. We quantify these gene-activity bursts using single-molecule-resolution mRNA measurements in individual cells, analyzed using a stochastic mathematical model of the gene-network kinetics. The quantitative relation between stability and gene activity is independent of the fine details of gene regulation, suggesting that a quantitative prediction of cell-state stability may also be possible in more complex systems.
Assuntos
Regulação Bacteriana da Expressão Gênica/fisiologia , Instabilidade Genômica/genética , Lisogenia/genética , Proteínas Repressoras/fisiologia , Proteínas Virais Reguladoras e Acessórias/fisiologia , Bacteriófago lambda/genética , Bacteriófago lambda/fisiologia , Escherichia coli/genética , Escherichia coli/fisiologia , Regulação Bacteriana da Expressão Gênica/genética , Genes Virais/fisiologia , Genoma Bacteriano/fisiologia , Modelos Biológicos , Organismos Geneticamente Modificados , Proteínas Repressoras/genética , Proteínas Virais Reguladoras e Acessórias/genéticaRESUMO
Gene activity is described by the time series of discrete, stochastic mRNA production events. This transcriptional time series shows intermittent, bursty behavior. One consequence of this temporal intricacy is that gene expression can be tuned by varying different features of the time series. Here we quantify copy-number statistics of mRNA from 20 Escherichia coli promoters using single-molecule fluorescence in situ hybridization in order to characterize the general properties of these transcriptional time series. We find that the degree of burstiness is correlated with gene expression level but is largely independent of other parameters of gene regulation. The observed behavior can be explained by the underlying variation in the duration of bursting events. Using Shannon's mutual information function, we estimate the mutual information transmitted between an outside stimulus, such as the extracellular concentration of inducer molecules, and intracellular levels of mRNA. This suggests that the outside stimulus transmits information reflected in the properties of transcriptional time series.