| Title: | A predictive model of gene expression reveals the role of network motifs in the mating response of yeast |
| Author(s): | Pomeroy AE; Pena MI; Houser JR; Dixit G; Dohlman HG; Elston TC; Errede B; |
| Address: | "Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. errede@email.unc.edu telston@med.unc.edu. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. errede@email.unc.edu telston@med.unc.edu. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Computational Medicine Program, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. errede@email.unc.edu telston@med.unc.edu" |
| DOI: | 10.1126/scisignal.abb5235 |
| ISSN/ISBN: | 1937-9145 (Electronic) 1945-0877 (Print) 1945-0877 (Linking) |
| Abstract: | "Cells use signaling pathways to receive and process information about their environment. These nonlinear systems rely on feedback and feedforward regulation to respond appropriately to changing environmental conditions. Mathematical models describing signaling pathways often lack predictive power because they are not trained on data that encompass the diverse time scales on which these regulatory mechanisms operate. We addressed this limitation by measuring transcriptional changes induced by the mating response in Saccharomyces cerevisiae exposed to different dynamic patterns of pheromone. We found that pheromone-induced transcription persisted after pheromone removal and showed long-term adaptation upon sustained pheromone exposure. We developed a model of the regulatory network that captured both characteristics of the mating response. We fit this model to experimental data with an evolutionary algorithm and used the parameterized model to predict scenarios for which it was not trained, including different temporal stimulus profiles and genetic perturbations to pathway components. Our model allowed us to establish the role of four architectural elements of the network in regulating gene expression. These network motifs are incoherent feedforward, positive feedback, negative feedback, and repressor binding. Experimental and computational perturbations to these network motifs established a specific role for each in coordinating the mating response to persistent and dynamic stimulation" |
| Keywords: | "Gene Expression Gene Expression Regulation, Fungal Pheromones *Saccharomyces cerevisiae/genetics/metabolism *Saccharomyces cerevisiae Proteins/genetics/metabolism;" |
| Notes: | "MedlinePomeroy, Amy E Pena, Matthew I Houser, John R Dixit, Gauri Dohlman, Henrik G Elston, Timothy C Errede, Beverly eng R01 GM114136/GM/NIGMS NIH HHS/ R35 GM118105/GM/NIGMS NIH HHS/ R35 GM127145/GM/NIGMS NIH HHS/ T32 GM067553/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2021/02/18 Sci Signal. 2021 Feb 16; 14(670):eabb5235. doi: 10.1126/scisignal.abb5235" |
