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Science 332 (6030): 732-735

Copyright © 2011 by the American Association for the Advancement of Science

Transient Activation of the HOG MAPK Pathway Regulates Bimodal Gene Expression

Serge Pelet,1,* Fabian Rudolf,1,{dagger} Mariona Nadal-Ribelles,2 Eulàlia de Nadal,2 Francesc Posas,2 Matthias Peter1,*

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.

1 ETH-Zurich, Department of Biology, Institute of Biochemistry, Schafmattstrasse 18, CH-8093 Zurich, Switzerland.
2 Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, E-08003 Barcelona, Spain.

{dagger} Present address: D-BSSE, ETH-Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.

* To whom correspondence should be addressed. E-mail: serge.pelet{at}bc.biol.ethz.ch (S.P.); matthias.peter{at}bc.biol.ethz.ch (M.P.)

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