Department of Physics, University of Illinois, Urbana, IL, USA.
Mol Syst Biol. 2010 Nov 30;6:440. doi: 10.1038/msb.2010.96.
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.
活细胞维持其基因表达状态可遗传记忆的能力是细胞分化的关键。细菌溶原性为长期细胞记忆提供了一个简单的范例。在这项研究中，我们解决了以下问题：在没有外部干扰的情况下，细胞在自发脱离该状态之前会在溶原状态下停留多长时间？我们通过直接测量表明，溶原稳定性与决定命运的基因 cI 的活性爆发频率呈简单的指数关系。我们使用单个分子分辨率的 mRNA 测量来量化这些基因活性爆发，并使用基因网络动力学的随机数学模型进行分析。稳定性与基因活性之间的定量关系与基因调控的细节无关，这表明在更复杂的系统中也可能对细胞状态的稳定性进行定量预测。
