Shared control of gene expression in bacteria by transcription factors and global physiology of the cell
Shared control of gene expression in bacteria by transcription factors and global physiology of the cell
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DOI：
10.1038/msb.2012.70
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发表时间：
2013-01-01
影响因子：
9.9
通讯作者：
Geiselmann, Johannes
中科院分区：
文献类型：
--
作者：
Berthoumieux, Sara;de Jong, Hidde;Geiselmann, Johannes
基因表达受以下因素的联合作用控制：（i）细胞的整体生理状态，特别是基因表达机制的活性，和（ii）DNA结合转录因子和其他特异性调节因子。我们提出了一个基于模型的方法来区分这两种影响，使用时间分辨测量启动子活动。我们通过分析大肠杆菌中碳代谢调控所涉及的回路来证明该方法的优势。杆菌我们的研究结果表明，网络的转录反应是由细胞的生理状态和信号代谢产物环磷酸腺苷（cAMP）。转录因子缺乏强调控作用表明，它们不是生长转换过程中基因表达变化的主要协调者，而是它们补充了全局生理控制机制的作用。这种观点的变化对转录组数据的解释以及生物技术和合成生物学中生物网络的设计具有重要影响。Molecular Systems Biology 9：634; 2013年1月22日在线发表; doi：10.1038/msb.2012.70
Gene expression is controlled by the joint effect of (i) the global physiological state of the cell, in particular the activity of the gene expression machinery, and (ii) DNA-binding transcription factors and other specific regulators. We present a model-based approach to distinguish between these two effects using time-resolved measurements of promoter activities. We demonstrate the strength of the approach by analyzing a circuit involved in the regulation of carbon metabolism in E. coli. Our results show that the transcriptional response of the network is controlled by the physiological state of the cell and the signaling metabolite cyclic AMP (cAMP). The absence of a strong regulatory effect of transcription factors suggests that they are not the main coordinators of gene expression changes during growth transitions, but rather that they complement the effect of global physiological control mechanisms. This change of perspective has important consequences for the interpretation of transcriptome data and the design of biological networks in biotechnology and synthetic biology. Molecular Systems Biology 9: 634; published online 22 January 2013; doi:10.1038/msb.2012.70