Quantitative kinetic analysis of the bacteriophage λ genetic network
Quantitative kinetic analysis of the bacteriophage λ genetic network
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DOI：
10.1073/pnas.0500670102
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发表时间：
2005-03-22
影响因子：
11.1
通讯作者：
Oppenheim, AB
中科院分区：
文献类型：
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作者：
Kobiler, O;Rokney, A;Oppenheim, AB
噬菌体 A 的裂解-溶原决策一直是发育遗传网络的范例，该网络由互锁的正反馈环和负反馈环组成。该遗传网络能够对环境信号和感染噬菌体的数量做出反应。 Cl 和 Cro 功能之间的相互作用表明了裂解-溶源决策的双稳态开关模型。在这里，我们以前所未有的时间分辨率展示了裂解和溶原途径执行的实时图片。我们在体内监测 CII 和 Q 基因调节因子的水平和功能。这些激活剂是共转录的，但控制相反的发育途径。有利于溶原反应的条件显示出 Q 活性的严重延迟和下调，无论是 CII 依赖型还是 CII 独立型。尽管 CII 活性与其蛋白质水平相关，但 Q 在观察到其功能之前显示出明显的阈值。我们的定量分析表明，通过调节 CII 和 CIII，Cro 在 A 遗传网络感知感染细胞的一种和多种噬菌体颗粒之间差异的能力中发挥着关键作用。因此，我们的结果提供了一个改进的框架来解释决策过程中长期存在的难题。
The lysis-lysogeny decision of bacteriophage A has been a paradigm for a developmental genetic network, which is composed of interlocked positive and negative feedback loops. This genetic network is capable of responding to environmental signals and to the number of infecting phages. An interplay between Cl and Cro functions suggested a bistable switch model for the lysis-lysogeny decision. Here, we present a real-time picture of the execution of lytic and lysogenic pathways with unprecedented temporal resolution. We monitor, in vivo, both the level and function of the CII and Q gene regulators. These activators are cotranscribed yet control opposite developmental pathways. Conditions that favor the lysogenic response show severe delay and down-regulation of Q activity, in both CII-dependent and CII-independent ways. Whereas CII activity correlates with its protein level, Q shows a pronounced threshold before its function is observed. Our quantitative analyses suggest that by regulating CII and CIII, Cro plays a key role in the ability of the A genetic network to sense the difference between one and more than one phage particles infecting a cell. Thus, our results provide an improved framework to explain the longstanding puzzle of the decision process.