Multiscale effects of heating and cooling on genes and gene networks

Most organisms must cope with temperature changes. This involves genes and gene networks both as subjects and agents of cellular protection, creating difficulties in understanding. Here, we study how heating and cooling affect expression of single genes and synthetic gene circuits in We discovered t...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 45; p. E10797
Main Authors: Charlebois, Daniel A, Hauser, Kevin, Marshall, Sylvia, Balázsi, Gábor
Format: Journal Article
Language:English
Published: United States 06.11.2018
Subjects:
Adaptation, Physiological - genetics
Cell Cycle Checkpoints - genetics
Cold Temperature
Fungal Proteins - genetics
Fungal Proteins - metabolism
Gene Expression Regulation, Fungal
Gene Regulatory Networks
Genes, Reporter
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
Hot Temperature
Repressor Proteins - genetics
Repressor Proteins - metabolism
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Stress, Physiological
Thermodynamics
noise
temperature
feedback regulation
synthetic gene circuit
cellular decision
ISSN:1091-6490, 1091-6490
Online Access:Get more information
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Summary:Most organisms must cope with temperature changes. This involves genes and gene networks both as subjects and agents of cellular protection, creating difficulties in understanding. Here, we study how heating and cooling affect expression of single genes and synthetic gene circuits in We discovered that nonoptimal temperatures induce a cell fate choice between stress resistance and growth arrest. This creates dramatic gene expression bimodality in isogenic cell populations, as arrest abolishes gene expression. Multiscale models incorporating population dynamics, temperature-dependent growth rates, and Arrhenius scaling of reaction rates captured the effects of cooling, but not those of heating in resistant cells. Molecular-dynamics simulations revealed how heating alters the conformational dynamics of the TetR repressor, fully explaining the experimental observations. Overall, nonoptimal temperatures induce a cell fate decision and corrupt gene and gene network function in computationally predictable ways, which may aid future applications of engineered microbes in nonstandard temperatures.
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1810858115