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Sci Adv. 2018 Apr 18;4(4):e1701775. doi: 10.1126/sciadv.1701775. eCollection 2018 Apr.

Heritable stress response dynamics revealed by single-cell genealogy.

Chatterjee M1,2, Acar M2,3,4,5.

Author information

Department of Electrical Engineering, Yale University, 10 Hillhouse Avenue, New Haven, CT 06520, USA.
Systems Biology Institute, Yale University, 850 West Campus Drive, West Haven, CT 06516, USA.
Department of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT 06511, USA.
Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, 300 George Street, Suite 501, New Haven, CT 06511, USA.
Department of Physics, Yale University, 217 Prospect Street, New Haven, CT 06511, USA.


Cells often respond to environmental stimuli by activating specific transcription factors. Upon exposure to glucose limitation stress, it is known that yeast Saccharomyces cerevisiae cells dephosphorylate the general stress response factor Msn2, leading to its nuclear localization, which in turn activates the expression of many genes. However, the precise dynamics of Msn2 nucleocytoplasmic translocations and whether they are inherited over multiple generations in a stress-dependent manner are not well understood. Tracking Msn2 localization events in yeast lineages grown on a microfluidic chip, here we report how cells modulate the amplitude, duration, frequency, and dynamic pattern of the localization events in response to glucose limitation stress. Single yeast cells were found to modulate the amplitude and frequency of Msn2 nuclear localization, but not its duration. Moreover, the Msn2 localization frequency was epigenetically inherited in descendants of mother cells, leading to a decrease in cell-to-cell variation in localization frequency. An analysis of the time dynamic patterns of nuclear localizations between genealogically related cell pairs using an information theory approach found that the magnitude of pattern similarity increased with stress intensity and was strongly inherited by the descendant cells at the highest stress level. By dissecting how general stress response dynamics is contributed by different modulation schemes over long time scales, our work provides insight into which scheme evolution might have acted on to optimize fitness in stressful environments.

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