Functional effects of heating and cooling gene networks

Abstract

Everyday existence and survival of most organisms requires coping with temperature changes, which involves gene regulatory networks both as subjects and agents of cellular protection. Yet, how temperature affects gene network function remains unclear, partly because natural gene networks are complex and incompletely characterized. Here, we study how heating and cooling affect the function of single genes and well-characterized synthetic gene circuits in Saccharomyces cerevisiae. We found nontrivial, nonmonotone temperature-dependent gene expression trends at non-growth-optimal temperatures. In addition, heating caused unusual bimodality in the negative-feedback gene circuit expression and shifts upward the bimodal regime for the positive feedback gene circuit. Mathematical models incorporating temperature-dependent growth rates and Arrhenius scaling of reaction rates captured the effects of cooling, but not those of heating. Molecular dynamics simulations revealed that heating alters the conformational dynamics and allows DNA-binding of the TetR transcriptional repressor, fully explaining the experimental results for the negative-feedback gene circuit. Overall, we uncover how temperature shifts may corrupt gene networks, which may aid future designs of temperature-robust synthetic gene circuits.