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Signal-dependent dynamics of transcription factor translocation controls gene expression

Nature Structural & Molecular Biology volume 19, pages 3139 (2012) | Download Citation


Information about environmental stimuli is often transmitted using common signaling molecules, but the mechanisms that ensure signaling specificity are not entirely known. Here 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 Saccharomyces cerevisiae general stress response transcription factor Msn2. Through artificial control of the dynamics of Msn2 translocation, we reveal how distinct dynamical 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 transcription factor binding properties. Thus, multiple environmental signals can trigger qualitatively different dynamics of a single transcription factor and influence gene expression patterns.

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We thank S. Ramanathan for help with the microfluidics devices. We thank P. Cluzel, V. Denic, G. Lahav, M. Springer, B. Stern, H. Dohlman, T. Elston and M. Behar for critical comments on the manuscript. We thank X. Zhou in the O'Shea lab for generously providing the unpublished nucleosome profile data, M. Rust and S. Mukherji for insightful suggestions, and other members of the O'Shea lab for helpful discussions. E.K.O. is a Howard Hughes Medical Institute investigator.

Author information


  1. Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA.

    • Nan Hao
    •  & Erin K O'Shea
  2. Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.

    • Nan Hao
    •  & Erin K O'Shea
  3. Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.

    • Nan Hao
    •  & Erin K O'Shea
  4. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.

    • Erin K O'Shea


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N.H. and E.K.O. designed the project. N.H. carried out the experiments and analyzed the data. N.H. and E.K.O. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Erin K O'Shea.

Supplementary information

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  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–15, Supplementary Results and Supplementary Methods


  1. 1.

    Supplementary Video 1

    Time-lapse video of Msn2-YFP in response to 0.1% glucose limitation.

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    Supplementary Video 2

    Time-lapse video of Msn2-YFP in response to 0.375 M KCl.

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    Supplementary Video 3

    Time-lapse video of Msn2-YFP in response to 0.01 mM H2O2.

  4. 4.

    Supplementary Video 4

    Time-lapse video of Msn2-YFP in response to oscillatory 1-NM-PP1 treatment.

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