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Combinatorial gene regulation by modulation of relative pulse timing

Author

Listed:
  • Yihan Lin

    (Howard Hughes Medical Institute, California Institute of Technology
    California Institute of Technology)

  • Chang Ho Sohn

    (California Institute of Technology)

  • Chiraj K. Dalal

    (Howard Hughes Medical Institute, California Institute of Technology
    California Institute of Technology
    † Present address: Department of Microbiology and Immunology, UCSF, San Francisco, California 94143, USA.)

  • Long Cai

    (California Institute of Technology)

  • Michael B. Elowitz

    (Howard Hughes Medical Institute, California Institute of Technology
    California Institute of Technology)

Abstract

Studies of individual living cells have revealed that many transcription factors activate in dynamic, and often stochastic, pulses within the same cell. However, it has remained unclear whether cells might exploit the dynamic interaction of these pulses to control gene expression. Here, using quantitative single-cell time-lapse imaging of Saccharomyces cerevisiae, we show that the pulsatile transcription factors Msn2 and Mig1 combinatorially regulate their target genes through modulation of their relative pulse timing. The activator Msn2 and repressor Mig1 showed pulsed activation in either a temporally overlapping or non-overlapping manner during their transient response to different inputs, with only the non-overlapping dynamics efficiently activating target gene expression. Similarly, under constant environmental conditions, where Msn2 and Mig1 exhibit sporadic pulsing, glucose concentration modulated the temporal overlap between pulses of the two factors. Together, these results reveal a time-based mode of combinatorial gene regulation. Regulation through relative signal timing is common in engineering and neurobiology, and these results suggest that it could also function broadly within the signalling and regulatory systems of the cell.

Suggested Citation

  • Yihan Lin & Chang Ho Sohn & Chiraj K. Dalal & Long Cai & Michael B. Elowitz, 2015. "Combinatorial gene regulation by modulation of relative pulse timing," Nature, Nature, vol. 527(7576), pages 54-58, November.
    • Handle: RePEc:nat:nature:v:527:y:2015:i:7576:d:10.1038_nature15710
    DOI: 10.1038/nature15710
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    Cited by:

    1. C Caranica & A Al-Omari & Z Deng & J Griffith & R Nilsen & L Mao & J Arnold & H-B Schüttler, 2018. "Ensemble methods for stochastic networks with special reference to the biological clock of Neurospora crassa," PLOS ONE, Public Library of Science, vol. 13(5), pages 1-28, May.
    2. Jonathan Desponds & Huy Tran & Teresa Ferraro & Tanguy Lucas & Carmina Perez Romero & Aurelien Guillou & Cecile Fradin & Mathieu Coppey & Nathalie Dostatni & Aleksandra M Walczak, 2016. "Precision of Readout at the hunchback Gene: Analyzing Short Transcription Time Traces in Living Fly Embryos," PLOS Computational Biology, Public Library of Science, vol. 12(12), pages 1-31, December.

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