4.8 Article

Decoupling transcription factor expression and activity enables dimmer switch gene regulation

期刊

SCIENCE
卷 372, 期 6539, 页码 292-+

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aba7582

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资金

  1. NIH [R01-GM120122-03]
  2. National Science Foundation Graduate Research Fellowship [DGE1144152]
  3. National Science Foundation [1349248]
  4. Div Of Molecular and Cellular Bioscience
  5. Direct For Biological Sciences [1349248] Funding Source: National Science Foundation

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Gene-regulatory networks achieve complex mappings of inputs to outputs through mechanisms that are poorly understood. In the galactose-responsive pathway in Saccharomyces cerevisiae, the decision to activate transcription of genes encoding pathway components is controlled independently from the expression level, resembling a mechanical dimmer switch. Hierarchical regulation of a single transcription factor enables dimmer switch gene regulation, allowing cells to fine-tune responses to multi-input environments on physiological and evolutionary time scales.
Gene-regulatory networks achieve complex mappings of inputs to outputs through mechanisms that are poorly understood. We found that in the galactose-responsive pathway in Saccharomyces cerevisiae, the decision to activate the transcription of genes encoding pathway components is controlled independently from the expression level, resulting in behavior resembling that of a mechanical dimmer switch. This was not a direct result of chromatin regulation or combinatorial control at galactose-responsive promoters; rather, this behavior was achieved by hierarchical regulation of the expression and activity of a single transcription factor. Hierarchical regulation is ubiquitous, and thus dimmer switch regulation is likely a key feature of many biological systems. Dimmer switch gene regulation may allow cells to fine-tune their responses to multi-input environments on both physiological and evolutionary time scales.

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