title: Transient activation of the HOG MAPK pathway regulates bimodal gene expression.
abstract: Mitogen-activated protein kinase (MAPK) cascades are conserved signaling modules that control many cellular processes by integrating intra- and extracellular cues. The p38/Hog1 MAPK is transiently activated in response to osmotic stress, leading to rapid translocation into the nucleus and induction of a specific transcriptional program. When investigating the dynamic interplay between Hog1 activation and Hog1-driven gene expression, we found that Hog1 activation increases linearly with stimulus, whereas the transcriptional output is bimodal. Modeling predictions, corroborated by single-cell experiments, established that a slow stochastic transition from a repressed to an activated transcriptional state in conjunction with transient Hog1 activation generates this behavior. Together, these findings provide a molecular mechanism by which a cell can impose a transcriptional threshold in response to a linear signaling behavior.
authors.affiliation: ETH-Zurich, Department of Biology, Institute of Biochemistry, Schafmattstrasse 18, CH-8093 Zurich, Switzerland. serge.pelet@bc.biol.ethz.ch
authors.forename: Serge
authors.initials: S
authors.lastname: Pelet
authors.forename: Fabian
authors.initials: F
authors.lastname: Rudolf
authors.forename: Mariona
authors.initials: M
authors.lastname: Nadal-Ribelles
authors.forename: Eulàlia
authors.initials: E
authors.lastname: de Nadal
authors.forename: Francesc
authors.initials: F
authors.lastname: Posas
authors.forename: Matthias
authors.initials: M
authors.lastname: Peter
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004789:Enzyme Activation; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008957:Models, Genetic; D009994:Osmolar Concentration; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013269:Stochastic Processes; D013312:Stress, Physiological; D015533:Transcriptional Activation
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases