Identification of regulatory network topological units coordinating the genome-wide transcriptional response to glucose in Escherichia coli.
Identification of regulatory network topological units coordinating the genome-wide transcriptional response to glucose in Escherichia coli.
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DOI：
10.1186/1471-2180-7-53
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发表时间：
2007-06-08
期刊：
影响因子：
4.2
通讯作者：
Gosset G
中科院分区：
文献类型：
--
作者：
Gutierrez-Ríos RM;Freyre-Gonzalez JA;Resendis O;Collado-Vides J;Saier M;Gosset G
葡萄糖是大肠杆菌首选的碳和能量来源。一个复杂的调节网络协调基因表达、运输和酶活性，以响应这种糖的存在。为了确定细胞对葡萄糖的反应程度，我们采用了一种结合全球转录组和调控网络分析的方法。分析在Luria-Bertani培养基（LB）或LB+ 4 g/L葡萄糖（LB+ g）中生长的等基因野生型和crp-菌株的转录组数据，以鉴定差异转录基因。我们分别检测到180个和200个基因在葡萄糖存在下表现出相对转录水平的增加和减少。在LB中观察到的表达模式与糖异生代谢状态一致，包括小分子和大分子的主动转运和相互转化，蛋白酶编码基因的诱导和部分热休克反应。在LB+G中，检测到分解代谢抑制转运和代谢相互转化活性。我们还检测到从头合成核苷酸、氨基酸和蛋白质的能力增加。一组基因的聚类分析显示，在LB+G中，CRP介导了大多数转录水平降低的基因的分解代谢物抑制，而Fis则参与了这种情况下基因的上调。从拓扑功能单元的角度对调控网络进行分析，揭示了8个相互连接的模块，再次揭示了Fis和CRP作为直接负责细胞协调反应的重要性。其他未广泛连接的转录因子（如FruR和PdhR）也出现了这种效应，考虑到介质组成，它们表现出一致的响应。这项工作确定了8个相互关联的调节网络模块，包括CRP、Fis和其他直接或间接响应葡萄糖存在的转录因子。在大多数情况下，这些模块中的每一个都包含编码生理相关功能的基因，从而表明调控网络拓扑与涉及营养感知和代谢的相关细胞功能之间存在联系。
Glucose is the preferred carbon and energy source for Escherichia coli. A complex regulatory network coordinates gene expression, transport and enzyme activities in response to the presence of this sugar. To determine the extent of the cellular response to glucose, we applied an approach combining global transcriptome and regulatory network analyses. Transcriptome data from isogenic wild type and crp- strains grown in Luria-Bertani medium (LB) or LB + 4 g/L glucose (LB+G) were analyzed to identify differentially transcribed genes. We detected 180 and 200 genes displaying increased and reduced relative transcript levels in the presence of glucose, respectively. The observed expression pattern in LB was consistent with a gluconeogenic metabolic state including active transport and interconversion of small molecules and macromolecules, induction of protease-encoding genes and a partial heat shock response. In LB+G, catabolic repression was detected for transport and metabolic interconversion activities. We also detected an increased capacity for de novo synthesis of nucleotides, amino acids and proteins. Cluster analysis of a subset of genes revealed that CRP mediates catabolite repression for most of the genes displaying reduced transcript levels in LB+G, whereas Fis participates in the upregulation of genes under this condition. An analysis of the regulatory network, in terms of topological functional units, revealed 8 interconnected modules which again exposed the importance of Fis and CRP as directly responsible for the coordinated response of the cell. This effect was also seen with other not extensively connected transcription factors such as FruR and PdhR, which showed a consistent response considering media composition. This work allowed the identification of eight interconnected regulatory network modules that includes CRP, Fis and other transcriptional factors that respond directly or indirectly to the presence of glucose. In most cases, each of these modules includes genes encoding physiologically related functions, thus indicating a connection between regulatory network topology and related cellular functions involved in nutrient sensing and metabolism.
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