Activity motifs reveal principles of timing in transcriptional control of the yeast metabolic network

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Abstract
Chechik et al. define activity motifs, which extend the concept of a network motif from the static to the dynamic realm. Mapping functional data onto network structure enables them to reveal new systems-level principles describing how yeast cells integrate exogenous signals and use transcriptional regulation to optimize metabolic responses to environmental perturbations. 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.