title: Encoding four gene expression programs in the activation dynamics of a single transcription factor.
abstract: Cellular signaling response pathways often exhibit a bow-tie topology [1,2]: multiple upstream stress signals converge on a single shared transcription factor, which is thought to induce different downstream gene expression programs (Figure 1A). However, if several different signals activate the same transcription factor, can each signal then induce a specific gene expression response? A growing body of literature supports a temporal coding theory where information about environmental signals can be encoded, at least partially, in the temporal dynamics of the shared transcription factor [1,2]. For example, in the case of the budding yeast transcription factor Msn2, different stresses induce distinct Msn2 activation dynamics: Msn2 shows pulsatile nuclear activation with dose-dependent frequency under glucose limitation, but sustained nuclear activation with dose-dependent amplitude under oxidative stress [3]. These dynamic patterns can then lead to differential gene expression responses [3-5], but it is not known how much specificity can be obtained. Thus, a major question of this temporal coding theory is how many gene response programs or cellular functions can be robustly encoded by dynamic control of a single transcription factor. Here we provide the first direct evidence that, simply by regulating the activation dynamics of a single transcription factor, it is possible to preferentially induce four distinct gene expression programs.
authors.affiliation: Department of Molecular Cell Biology, HHMI, Li Ka Shing Center, University of California, Berkeley, CA 94720, USA; Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Harvard University, Northwest Laboratory, 52 Oxford Street, Cambridge, MA 02138, USA; Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Northwest Laboratory, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Anders S
authors.initials: AS
authors.lastname: Hansen
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Harvard University, Northwest Laboratory, 52 Oxford Street, Cambridge, MA 02138, USA; Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Northwest Laboratory, 52 Oxford Street, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Northwest Laboratory, 52 Oxford Street, Cambridge, MA 02138, USA. Electronic address: erin_oshea@harvard.edu.
authors.forename: Erin K
authors.initials: EK
authors.lastname: O'Shea
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism; D005456:Fluorescent Dyes; D015966:Gene Expression Regulation, Fungal; D011401:Promoter Regions, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D004718:Saccharomycetales / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; C081935:MSN2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors