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Dynamic patterns of gene expression match extracellular signals through push-pull regulation.

Luis Fernando Montano-Gutierrez1, Marc Sturrock2, Iseabail L Farquhar1

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Cells precisely control gene expression using a novel push-pull regulatory network. This mechanism allows budding yeast to match hexose transporter gene expression to specific glucose concentrations, ensuring efficient nutrient utilization.

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Area of Science:

  • Molecular Biology
  • Systems Biology
  • Cellular Regulation

Background:

  • Cells exhibit remarkable ability to adjust gene expression in response to environmental signals.
  • Budding yeast, for instance, utilizes at least seven hexose transporter genes, each tuned to specific extracellular glucose concentration ranges.

Purpose of the Study:

  • To elucidate the mechanistic basis of how budding yeast matches hexose transporter ([Formula: see text]) gene expression to varying extracellular glucose levels.
  • To investigate the role of a novel "push-pull" regulatory network in this process.

Main Methods:

  • Time-lapse microscopy
  • Microfluidics
  • Dynamic glucose perturbation experiments
  • Mathematical modeling
  • Analysis of transcription factor activity

Main Results:

  • A push-pull regulatory mechanism involving Mth1, Std1, Mig1, and Mig2 was identified. Rising glucose weakens repression by Mth1/Std1 while strengthening repression by Mig1/Mig2, and vice-versa for falling glucose.
  • The combined activity of these regulators effectively reports extracellular glucose concentrations.
  • Specific coupling between [Formula: see text] promoters and these regulators, based on transporter affinity (low, medium, high), enables precise expression matching.
  • Experimental rewiring of transcription demonstrated the ability to alter transporter gene response characteristics.

Conclusions:

  • The identified push-pull regulation is a key mechanism for matching gene expression to environmental signals like glucose concentration.
  • This regulatory strategy allows cells to fine-tune transporter expression for optimal nutrient uptake.
  • The principle of push-pull regulation is likely a widespread biological phenomenon with broad implications for gene expression control.