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Activity Motifs Reveal Principles of Timing in Transcriptional Control of the Yeast Metabolic Network

  • Gal Chechik
  • Eugene Oh
  • Oliver Rando
  • Jonathan Weissman
  • Aviv Regev
  • Daphne Koller
Nature Biotechnology, vol. 26 (11) (2008), pp. 1251-1259


Significant insight about biological networks arises from the study of network motifs—overly abundant network subgraphs, 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.

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