Dose dependent gene expression is dynamically modulated by the history, physiology and age of yeast cells

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Amparo Pascual-Ahuir
  • Eva González-Cantó
  • Pauline Juyoux
  • Julia Pable
  • Poveda Huertes, Daniel
  • Sandra Saiz-Balbastre
  • Sonia Squeo
  • Alvaro Ureña-Marco
  • Elena Vanacloig-Pedros
  • Laura Zaragoza-Infante
  • Markus Proft

Cells respond to external stimuli with transient gene expression changes in order to adapt to environmental alterations. However, the dose response profile of gene induction upon a given stress depends on many intrinsic and extrinsic factors. Here we show that the accurate quantification of dose dependent gene expression by live cell luciferase reporters reveals fundamental insights into stress signaling. We make the following discoveries applying this non-invasive reporter technology. (1) Signal transduction sensitivities can be compared and we apply this here to salt, oxidative and xenobiotic stress responsive transcription factors. (2) Stress signaling depends on where and how the damage is generated within the cell. Specifically we show that two ROS-generating agents, menadione and hydrogen peroxide, differ in their dependence on mitochondrial respiration. (3) Stress signaling is conditioned by the cells history. We demonstrate here that positive memory or an acquired resistance towards oxidative stress is induced dependent on the nature of the previous stress experience. (4) The metabolic state of the cell impinges on the sensitivity of stress signaling. This is shown here for the shift towards higher stress doses of the response profile for yeast cells moved from complex to synthetic medium. (5) The age of the cell conditions its transcriptional response capacity, which is demonstrated by the changes of the dose response to oxidative stress during both replicative and chronological aging. We conclude that capturing dose dependent gene expression in real time will be of invaluable help to understand stress signaling and its dynamic modulation.

OriginalsprogEngelsk
TidsskriftBBA Gene Regulatory Mechanisms
Vol/bind1862
Udgave nummer4
Sider (fra-til)457-471
Antal sider15
ISSN1874-9399
DOI
StatusUdgivet - 2019
Eksternt udgivetJa

Bibliografisk note

Copyright © 2019 Elsevier B.V. All rights reserved.

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