Transient activation of the HOG MAPK pathway regulates bimodal gene expression

Science
Serge PeletMatthias Peter

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.

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Citations

Jan 11, 2012·Integrative Biology : Quantitative Biosciences From Nano to Macro·Sung Sik LeeMatthias Peter
Sep 15, 2012·Integrative Biology : Quantitative Biosciences From Nano to Macro·Serge PeletMatthias Peter
Mar 9, 2013·Molecular BioSystems·Sonja LehtinenVera Pancaldi
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