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Principles of transcriptional control in the metabolic network of Saccharomyces cerevisiae

Nature Biotechnology volume 22, pages 86–92 (2004)Cite this article

Abstract

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.

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Figure 1: Correlation between genes of the same metabolic pathway.
Figure 2: Coexpressed enzymes often catalyze a linear chain of reactions.
Figure 3: Differential regulation of isozymes.
Figure 4: Hierarchical modularity in the metabolic network.

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Acknowledgements

We thank Sven Bergmann, Avigdor Eldar and Benny Shilo for comments on the manuscript. This work was supported by US National Institutes of Health grant no. A150562, by the Israeli Science Ministry and by the Y. Leon Benoziyo Institute for Molecular Medicine. N.B. is the incumbent of the Soretta and Henry Shapiro career development chair at the Weizmann Institute of Science.

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  1. Jan Ihmels and Ronen Levy: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel

    Jan Ihmels, Ronen Levy & Naama Barkai

  2. Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, 76100, Israel

    Naama Barkai

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  1. Jan Ihmels
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  2. Ronen Levy
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Correspondence to Naama Barkai.

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Ihmels, J., Levy, R. & Barkai, N. Principles of transcriptional control in the metabolic network of Saccharomyces cerevisiae. Nat Biotechnol 22, 86–92 (2004). https://doi.org/10.1038/nbt918

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