Abstract：Information about environmental stimuli is often transmitted using common signalling molecules, but the mechanisms that ensure signalling specificity are not entirely known. We show that the identities and intensities of different stresses are transmitted by modulation of the amplitude, duration or frequency of nuclear translocation of the budding yeast general stress responsive transcription factor (TF) Msn2. We explored how TFs process signaling inputs to generate diverse dynamic responses. Msn2 acted as a tunable signal processor that could track, filter, or integrate signals in an input dependent manner. This tunable signal processing originates from dual regulation of both nuclear import and export by phosphorylation, as mutants with one form of regulation sustained only one signal processing function. Versatile signal processing by Msn2 is crucial for generating distinct dynamic responses to different natural stresses. We also explored how distinct dynamics of Msn2 translocation differentially affected reporter gene expression. Using a simple model, we predicted stress-induced reporter gene expression from single-cell translocation dynamics. We then demonstrated that the response of natural target genes to dynamical modulation of Msn2 translocation is influenced by differences in the kinetics of promoter transitions and transcription factor binding properties. Thus, multiple environmental signals can trigger qualitatively different dynamics of a single transcription factor, and influence gene expression patterns.

Curriculum Vitae