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Science. 2011 May 6;332(6030):732-5. doi: 10.1126/science.1198851.

Transient activation of the HOG MAPK pathway regulates bimodal gene expression.

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ETH-Zurich, Department of Biology, Institute of Biochemistry, Schafmattstrasse 18, CH-8093 Zurich, Switzerland.


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.

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