Research ArticleSystems Biology

A predictive model of gene expression reveals the role of network motifs in the mating response of yeast

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Science Signaling  16 Feb 2021:
Vol. 14, Issue 670, eabb5235
DOI: 10.1126/scisignal.abb5235

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Motifs in mating responses

In the mating response in yeast, pheromone stimulation initiates a MAPK signaling cascade that alleviates the repression of the transcription factor Ste12 by Dig1 and Dig2, resulting in transcriptional changes, and that activates a factor called Far1, which promotes Ste12 degradation. Pomeroy et al. found that pheromone-induced transcriptional regulation showed persistence after pheromone removal and long-term adaptation upon prolonged pheromone exposure. They generated a model trained on transcriptional data generated in response to different temporal patterns of pheromone stimulation. The model predicted that persistence and long-term adaptation required four network motifs: feedforward, positive feedback, and negative feedback loops between MAPKs, Ste12, and Far1; and the rebinding of Dig1 and Dig2 to Ste12. These predictions were experimentally validated with mutant yeast strains. Thus, multiple network motifs ensure that gene expression is appropriately regulated in response to different patterns of pheromone exposure.

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