Analysis abstract
Nature Biotechnology 26, 1251 - 1259 (2008)
Published online: 26 October 2008 | doi:10.1038/nbt.1499
Activity motifs reveal principles of timing in transcriptional control of the yeast metabolic network
Gal Chechik1,5, Eugene Oh2, Oliver Rando3, Jonathan Weissman2, Aviv Regev4 & Daphne Koller1
Abstract
Significant insight about biological networks arises from the study of network motifs—overly abundant network subgraphs1, 2—but such wiring patterns do not specify when and how potential routes within a cellular network are used. To address this limitation, we introduce activity motifs, which capture patterns in the dynamic use of a network. Using this framework to analyze transcription in Saccharomyces cerevisiae metabolism, we find that cells use different timing activity motifs to optimize transcription timing in response to changing conditions: forward activation to produce metabolic compounds efficiently, backward shutoff to rapidly stop production of a detrimental product and synchronized activation for co-production of metabolites required for the same reaction. Measuring protein abundance over a time course reveals that mRNA timing motifs also occur at the protein level. Timing motifs significantly overlap with binding activity motifs, where genes in a linear chain have ordered binding affinity to a transcription factor, suggesting a mechanism for ordered transcription. Finely timed transcriptional regulation is therefore abundant in yeast metabolism, optimizing the organism's adaptation to new environmental conditions.
- Department of Computer Science, Stanford University, Stanford, California 94305, USA.
- Howard Hughes Medical Foundation and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California 94143, USA.
- Departments of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
- Department of Biology, Massachusetts Institute of Technology and the Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
- Present address: Google Research, 1600 Amphitheater Parkway, Mountain View, California 94043, USA.
Correspondence to: Aviv Regev4 e-mail: aregev@broad.mit.edu;
Correspondence to: Daphne Koller1 e-mail: koller@cs.stanford.edu
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