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首页> 外文期刊>Nature >Predicting expression patterns from regulatory sequence in Drosophila segmentation
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Predicting expression patterns from regulatory sequence in Drosophila segmentation

机译：果蝇分割中调控序列预测表达模式

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摘要

The establishment of complex expression patterns at precise times and locations is key to metazoan development, yet a mechanistic understanding of the underlying transcription control networks is still missing. Here we describe a novel thermodynamic model that computes expression patterns as a function of cis-regulatory sequence and of the binding-site preferences and expression of participating transcription factors. We apply this model to the segmentation gene network of Drosophila melanogaster and find that it predicts expression patterns of cis-regulatory modules with remarkable accuracy, demonstrating that positional information is encoded in the regulatory sequence and input factor distribution. Our analysis reveals that both strong and weaker binding sites contribute, leading to high occupancy of the module DNA, and conferring robustness against mutation; short-range homotypic clustering of weaker sites facilitates cooperative binding, which is necessary to sharpen the patterns. Our computational framework is generally applicable to most protein-DNA interaction systems.
机译：在精确的时间和位置建立复杂的表达模式是后生动物发展的关键，但是仍然缺乏对基本转录控制网络的机械理解。在这里，我们描述了一种新型的热力学模型，该模型计算表达模式作为顺式调节序列以及结合位点偏好和参与转录因子表达的函数。我们将该模型应用到果蝇的分割基因网络中，发现它以非常高的准确性预测了顺式调控模块的表达模式，表明位置信息编码在调控序列和输入因子分布中。我们的分析表明，强结合位点和弱结合位点都起作用，导致模块DNA的占用率高，并赋予了抵抗突变的鲁棒性。较弱位点的短距离同型聚类促进了协作结合，这对于锐化模式是必需的。我们的计算框架通常适用于大多数蛋白质-DNA相互作用系统。

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