Director, FAS Center for Systems Biology
Professor of Molecular and Cellular Biology and of Chemistry and Chemical Biology
Investigator, Howard Hughes Medical Institute
Reception follows seminar
Hao, N. and O'Shea, E. K.
Abstract: Living organisms respond to external cues and initiate appropriate physiological responses through signalling pathways that transmit signals to specific transcription factors, which regulate expression of target genes. In many cases, multiple inputs are transmitted by a common signalling component1-3. However the mechanisms that ensure specificity remain elusive. Here we show that the identities and intensities of different stresses are encoded by modulation of the amplitude, duration and/or frequency of nuclear translocation of the budding yeast general stress responsive transcription factor (TF) Msn2. Through artificial control of the dynamics of Msn2 nuclear translocation, we reveal how distinct dynamical modulation schemes differentially affect reporter gene expression. Using a simple model, we predict stress-induced reporter gene expression from single-cell translocation dynamics. We then demonstrate that the response of natural target genes to dynamical modulation of Msn2 translocation is influenced by differences in the kinetics of promoter transitions and TF binding properties. Thus, multiple environmental signals can be encoded in a single TF, and then decoded differently by different promoters to generate stimuli-specific gene expression patterns. Our findings represent a general strategy of information processing inside a cell and provide insights into the mechanisms underlying signalling specificity.