IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v527y2015i7576d10.1038_nature15710.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature15710
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature15710?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. 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.
    2. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:527:y:2015:i:7576:d:10.1038_nature15710. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.