Preferences in a trait decision determined by transcription factor variants

Area of Science:

• Molecular Biology
• Genetics
• Mycology

Background:

• Transcription factors regulate gene expression in response to environmental cues.
• In Saccharomyces cerevisiae, the transcription factor Ste12 controls the switch between mating and invasion phenotypes.
• Invasion specificity is mediated by Ste12 in cooperation with the cofactor Tec1.

Purpose of the Study:

• To investigate how variations in the Ste12 DNA-binding domain influence yeast's mating versus invasion preference.
• To understand the molecular mechanisms underlying Ste12's role in environmental adaptation.

Main Methods:

• Systematic analysis of thousands of Ste12 DNA-binding domain variants.
• Phenotypic assessment of yeast strains expressing Ste12 variants for mating and invasion capabilities.
• Characterization of DNA-binding specificity for wild-type and mutant Ste12 proteins.

Main Results:

• Single amino acid substitutions in the Ste12 DNA-binding domain can shift yeast phenotype towards mating or invasion.
• Mutations cluster in two distinct regions, implying alternative DNA-binding modes for each trait.
• Ste12 mutants promoting hyperinvasion bind unusual dimeric DNA sites independently of Tec1.

Conclusions:

• The Ste12 DNA-binding domain harbors critical sites that dictate cell fate decisions.
• Alternative DNA-binding modes of Ste12 likely facilitate adaptation to different environments.
• Ste12 may have independently evolved to activate invasion genes, explaining its role in Tec1-lacking fungal pathogens.