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Transient activation of the HOG MAPK pathway regulates bimodal gene expression


Pelet, S; Rudolf, F; Nadal-Ribelles, M; de Nadal, E; Posas, F; Peter, M (2011). Transient activation of the HOG MAPK pathway regulates bimodal gene expression. Science, 332(6030):732-735.

Abstract

Mitogen-activated protein kinase (MAPK) cascades are conserved signalling 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. Modelling 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 behaviour. Together, these findings provide a molecular mechanism by which a cell can impose a transcriptional threshold in response to a linear signalling behaviour.

Mitogen-activated protein kinase (MAPK) cascades are conserved signalling 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. Modelling 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 behaviour. Together, these findings provide a molecular mechanism by which a cell can impose a transcriptional threshold in response to a linear signalling behaviour.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:Special Collections > SystemsX.ch
Special Collections > SystemsX.ch > Research, Technology and Development Projects > YeastX
Special Collections > SystemsX.ch > Research, Technology and Development Projects
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2011
Deposited On:03 Jul 2013 17:58
Last Modified:05 Apr 2016 16:51
Publisher:American Association for the Advancement of Science
ISSN:0036-8075
Additional Information:This is the author's version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science {332, 10.1126/science.1198851}.
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1126/science.1198851
PubMed ID:21551064
Permanent URL: https://doi.org/10.5167/uzh-79117

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