Network motifs in the transcriptional regulation network of Escherichia coli
Network motifs in the transcriptional regulation network of Escherichia coli
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DOI：
10.1038/ng881
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发表时间：
2002-05-01
期刊：
影响因子：
30.8
通讯作者：
Alon, U
中科院分区：
文献类型：
--
作者：
Shen-Orr, SS;Milo, R;Alon, U
关于控制细胞中基因表达的转录调控网络的设计原理（1-10）知之甚少。然而，数据收集和分析的最新进展（2，11，12）正在产生关于基因调控网络的前所未有的信息量。为了理解这些复杂的布线图（1- 10，13），我们试图将这些网络分解为基本的构建块（2）。我们推广的概念，广泛用于序列分析，网络的水平。我们将“网络图案”定义为在网络的许多不同部分中以比随机网络中发现的频率高得多的频率重复出现的互连模式。我们应用新的算法系统地检测网络基序的最佳表征的调控网络之一，在大肠杆菌中的直接转录相互作用（3，6）。我们发现，网络的大部分是由三个高度显着的图案的重复出现。每个网络基序在决定基因表达方面具有特定的功能，例如产生时间表达程序和管理对波动的外部信号的反应。基序结构还允许对生物体的整个已知转录网络的容易解释的视图。这种方法可能有助于定义其他生物网络的基本计算元素。
Little is known about the design principles(1-10) of transcriptional regulation networks that control gene expression in cells. Recent advances in data collection and analysis(2,11,12), however, are generating unprecedented amounts of information about gene regulation networks. To understand these complex wiring diagrams(1-10,13), we sought to break down such networks into basic building blocks(2). We generalize the notion of motifs, widely used for sequence analysis, to the level of networks. We define 'network motifs' as patterns of interconnections that recur in many different parts of a network at frequencies much higher than those found in randomized networks. We applied new algorithms for systematically detecting network motifs to one of the best-characterized regulation networks, that of direct transcriptional interactions in Escherichia coli(3,6). We find that much of the network is composed of repeated appearances of three highly significant motifs. Each network motif has a specific function in determining gene expression, such as generating temporal expression programs and governing the responses to fluctuating external signals. The motif structure also allows an easily interpretable view of the entire known transcriptional network of the organism. This approach may help define the basic computational elements of other biological networks.