Functional architecture of Escherichia coli: new insights provided by a natural decomposition approach.
Functional architecture of Escherichia coli: new insights provided by a natural decomposition approach.
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DOI：
10.1186/gb-2008-9-10-r154
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发表时间：
2008-10-27
期刊：
影响因子：
12.3
通讯作者：
Collado-Vides J
中科院分区：
文献类型：
--
作者：
Freyre-González JA;Alonso-Pavón JA;Treviño-Quintanilla LG;Collado-Vides J
急诊大肠杆菌转录调控网络具有由转录因子控制的独立模块组成的非金字塔结构，其响应由模块间基因整合。以前的研究已经使用不同的方法，努力提取转录调控网络的模块化组织。然而，这些方法并不自然，因为它们试图将强连接的基因聚集到一个模块中，或者将已知的多效性转录因子定位在较低的层次中。在这里，我们解开大肠杆菌的转录调控网络，将其分离成关键元件，从而揭示其自然组织。我们还提出了一个数学标准，转录调控网络的拓扑特征的基础上，网络元素分为两个可能的类之一：层次或模块化基因。我们发现，模块化的基因聚集成生理相关的组验证的功能类的富集的统计分析。分级基因编码负责协调模块响应的转录因子的基础上一般利益的信号。层次元素与先前研究的全球监管机构高度相关，这表明这可能是第一个数学方法来确定全球监管机构。我们在转录调控网络中发现了一个以前从未描述过的新元素：模块间基因。这些结构基因在启动子水平上整合了来自不同模块的信号，因此来自不同的生理反应。利用多效性的概念，我们已经重建了网络的层次结构，并讨论了前馈基序在塑造转录调控网络的层次骨架中的作用。这项研究揭示了新的设计原则的基础上组织的转录调控网络，显示了一种新的非金字塔结构组成的独立模块全球管理的层次转录因子，其反应是由模块间基因整合。
The E. coli transcriptional regulatory network is shown to have a nonpyramidal architecture of independent modules governed by transcription factors, whose responses are integrated by intermodular genes. Previous studies have used different methods in an effort to extract the modular organization of transcriptional regulatory networks. However, these approaches are not natural, as they try to cluster strongly connected genes into a module or locate known pleiotropic transcription factors in lower hierarchical layers. Here, we unravel the transcriptional regulatory network of Escherichia coli by separating it into its key elements, thus revealing its natural organization. We also present a mathematical criterion, based on the topological features of the transcriptional regulatory network, to classify the network elements into one of two possible classes: hierarchical or modular genes. We found that modular genes are clustered into physiologically correlated groups validated by a statistical analysis of the enrichment of the functional classes. Hierarchical genes encode transcription factors responsible for coordinating module responses based on general interest signals. Hierarchical elements correlate highly with the previously studied global regulators, suggesting that this could be the first mathematical method to identify global regulators. We identified a new element in transcriptional regulatory networks never described before: intermodular genes. These are structural genes that integrate, at the promoter level, signals coming from different modules, and therefore from different physiological responses. Using the concept of pleiotropy, we have reconstructed the hierarchy of the network and discuss the role of feedforward motifs in shaping the hierarchical backbone of the transcriptional regulatory network. This study sheds new light on the design principles underpinning the organization of transcriptional regulatory networks, showing a novel nonpyramidal architecture composed of independent modules globally governed by hierarchical transcription factors, whose responses are integrated by intermodular genes.
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影响因子：
4.2
作者：
Gutierrez-Ríos RM;Freyre-Gonzalez JA;Resendis O;Collado-Vides J;Saier M;Gosset G
通讯作者：
Gosset G
DOI：
10.1006/bbrc.2002.6559
发表时间：
2002-03-08
影响因子：
3.1
作者：
Griffith, KL;Shah, IM;Wolf, RE
通讯作者：
Wolf, RE
影响因子：
5.6
作者：
Lavrrar, JL;Christoffersen, CA;McIntosh, MA
通讯作者：
McIntosh, MA
影响因子：
5.6
作者：
Griffith, KL;Wolf, RE
通讯作者：
Wolf, RE
影响因子：
64.8
作者：
Hartwell, LH;Hopfield, JJ;Murray, AW
通讯作者：
Murray, AW