Ihmels Jan, Levy Ronen, Barkai Naama
Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel.
Nat Biotechnol. 2004 Jan;22(1):86-92. doi: 10.1038/nbt918. Epub 2003 Nov 30.
Cellular networks are subject to extensive regulation, which modifies the availability and efficiency of connections between components in response to external conditions. Thus far, studies of large-scale networks have focused on their connectivity, but have not considered how the modulation of this connectivity might also determine network properties. To address this issue, we analyzed how the coordinated expression of enzymes shapes the metabolic network of Saccharomyces cerevisiae. By integrating large-scale expression data with the structural description of the metabolic network, we systematically characterized the transcriptional regulation of metabolic pathways. The analysis revealed recurrent patterns, which may represent design principles of metabolic gene regulation. First, we find that transcription regulation biases metabolic flow toward linearity by coexpressing only distinct branches at metabolic branchpoints. Second, individual isozymes were often separately coregulated with distinct processes, providing a means of reducing crosstalk between pathways using a common reaction. Finally, transcriptional regulation defined a hierarchical organization of metabolic pathways into groups of varying expression coherence. These results emphasize the utility of incorporating regulatory information when analyzing properties of large-scale cellular networks.
细胞网络受到广泛调控，这种调控会根据外部条件改变组件之间连接的可用性和效率。到目前为止，对大规模网络的研究主要集中在其连通性上，但尚未考虑这种连通性的调节如何也可能决定网络特性。为了解决这个问题，我们分析了酶的协同表达如何塑造酿酒酵母的代谢网络。通过将大规模表达数据与代谢网络的结构描述相结合，我们系统地表征了代谢途径的转录调控。分析揭示了反复出现的模式，这可能代表了代谢基因调控的设计原则。首先，我们发现转录调控通过仅在代谢分支点共表达不同的分支，使代谢流偏向线性。其次，单个同工酶通常与不同的过程分别进行共调控，这提供了一种减少使用共同反应的途径之间串扰的方法。最后，转录调控将代谢途径定义为具有不同表达一致性的组的层次组织。这些结果强调了在分析大规模细胞网络特性时纳入调控信息的实用性。
