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A Quantitative and Dynamic Model of the Arabidopsis Flowering Time Gene Regulatory Network

机译:拟南芥开花时间基因调控网络的定量和动态模型

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摘要

Various environmental signals integrate into a network of floral regulatory genes leading to the final decision on when to flower. Although a wealth of qualitative knowledge is available on how flowering time genes regulate each other, only a few studies incorporated this knowledge into predictive models. Such models are invaluable as they enable to investigate how various types of inputs are combined to give a quantitative readout. To investigate the effect of gene expression disturbances on flowering time, we developed a dynamic model for the regulation of flowering time in Arabidopsis thaliana. Model parameters were estimated based on expression time-courses for relevant genes, and a consistent set of flowering times for plants of various genetic backgrounds. Validation was performed by predicting changes in expression level in mutant backgrounds and comparing these predictions with independent expression data, and by comparison of predicted and experimental flowering times for several double mutants. Remarkably, the model predicts that a disturbance in a particular gene has not necessarily the largest impact on directly connected genes. For example, the model predicts that SUPPRESSOR OF OVEREXPRESSION OF CONSTANS (SOC1) mutation has a larger impact on APETALA1 (AP1), which is not directly regulated by SOC1, compared to its effect on LEAFY (LFY) which is under direct control of SOC1. This was confirmed by expression data. Another model prediction involves the importance of cooperativity in the regulation of APETALA1 (AP1) by LFY, a prediction supported by experimental evidence. Concluding, our model for flowering time gene regulation enables to address how different quantitative inputs are combined into one quantitative output, flowering time.
机译:各种环境信号整合到花卉调控基因的网络中,从而最终决定何时开花。尽管可以获得大量有关开花时间基因如何相互调控的定性知识,但只有少数研究将这种知识纳入了预测模型。这样的模型是无价的,因为它们能够研究各种类型的输入如何组合以给出定量的读数。为了研究基因表达障碍对开花时间的影响,我们开发了一个动态模型来调节拟南芥开花时间。根据相关基因的表达时程和各种遗传背景的植物的一致开花时间来估计模型参数。通过预测突变体背景中表达水平的变化,并将这些预测与独立表达数据进行比较,并通过比较几种双突变体的预测开花时间和实验开花时间来进行验证。值得注意的是,该模型预测特定基因的干扰不一定会对直接连接的基因产生最大的影响。例如,该模型预测,与其直接受SOC1控制的LEAFY(LFY)的影响相比,抑制过表达的CONSTANS(SOC1)突变对APETALA1(AP1)的影响更大,后者不受SOC1的直接调节。 。这由表达数据证实。另一个模型预测涉及LFY调节APETALA1(AP1)的协同作用的重要性,该证据得到了实验证据的支持。最后,我们的开花时间基因调控模型可以解决如何将不同的定量输入组合为一个定量输出即开花时间。

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