Extension of a genetic network model by iterative experimentation and mathematical analysis
Extension of a genetic network model by iterative experimentation and mathematical analysis
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DOI：
10.1038/msb4100018
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发表时间：
2005-01-01
影响因子：
9.9
通讯作者：
Millar, Andrew J.
中科院分区：
文献类型：
--
作者：
Locke, James C. W.;Southern, Megan M.;Millar, Andrew J.
生物钟包括产生关键基因节律性表达的反馈回路。高等植物拟南芥的分子遗传学研究揭示了一个复杂的时钟网络。该网络的第一部分是一个转录反馈回路，包括CAB表达1的时序（TOC1）、晚伸长下尾轴（LHY）和昼夜节律时钟相关1 (CCA1)，但未能解释重要的实验数据。我们开发了一个扩展模型，该模型基于更广泛的数据，并准确地预测了额外的实验结果。该模型包括与其他昼夜节律系统中实验确定的相媲美的连锁反馈回路。我们建议每个回路接收来自光的输入信号，并且每个回路包含一个尚未明确识别的假设组件。该模型的分析预测了这些成分的特性，包括黎明时被LHY和CCA1迅速抑制的急性光诱导。我们在晚间表达基因GIGANTEA （GI）的RNA水平中发现了这种意想不到的调控，支持了我们提出的网络，并使GI成为该成分的强有力候选。
Circadian clocks involve feedback loops that generate rhythmic expression of key genes. Molecular genetic studies in the higher plant Arabidopsis thaliana have revealed a complex clock network. The first part of the network to be identified, a transcriptional feedback loop comprising TIMING OF CAB EXPRESSION 1 (TOC1), LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), fails to account for significant experimental data. We develop an extended model that is based upon a wider range of data and accurately predicts additional experimental results. The model comprises interlocking feedback loops comparable to those identified experimentally in other circadian systems. We propose that each loop receives input signals from light, and that each loop includes a hypothetical component that had not been explicitly identified. Analysis of the model predicted the properties of these components, including an acute light induction at dawn that is rapidly repressed by LHY and CCA1. We found this unexpected regulation in RNA levels of the evening-expressed gene GIGANTEA (GI), supporting our proposed network and making GI a strong candidate for this component.