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Decoupling transcription factor expression and activity enables dimmer switch gene regulation

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Science  16 Apr 2021:
Vol. 372, Issue 6539, pp. 292-295
DOI: 10.1126/science.aba7582

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Circuit design for control of metabolism

A transcriptional control mechanism in yeast that allows cells to respond to changes in nutrient concentrations works very much like a household light-dimmer switch. That is, the system separately controls whether gene expression is “on” or “off” and the extent of gene expression. The galactose-responsive pathway is activated when yeast need to switch from metabolizing glucose to metabolizing galactose. Ricci-Tam et al. found that, rather than using two separate elements for the switch and dimmer controls, yeast use a single transcription factor, Gal4p, separately regulating its abundance (through transcriptional regulation) and its catalytic activity (through interaction with a protein-binding partner). Such regulation may be common and can allow responses to the environment on physiological and evolutionary time scales.

Science, this issue p. 292

Abstract

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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