1. Computational and Systems Biology
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Dynamic control of gene regulatory logic by seemingly redundant transcription factors

  1. Zohreh AkhavanAghdam
  2. Joydeb Sinha
  3. Omar P Tabbaa
  4. Nan Hao  Is a corresponding author
  1. University of California, San Diego, United States
Research Article
  • Cited 21
  • Views 2,847
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Cite this article as: eLife 2016;5:e18458 doi: 10.7554/eLife.18458

Abstract

Many transcription factors co-express with their homologs to regulate identical target genes, however the advantages of such redundancies remain elusive. Using single-cell imaging and microfluidics, we study the yeast general stress response transcription factor Msn2 and its seemingly redundant homolog Msn4. We find that gene regulation by these two factors is analogous to logic gate systems. Target genes with fast activation kinetics can be fully induced by either factor, behaving as an 'OR' gate. In contrast, target genes with slow activation kinetics behave as an 'AND' gate, requiring distinct contributions from both factors, upon transient stimulation. Furthermore, such genes become an 'OR' gate when the input duration is prolonged, suggesting that the logic gate scheme is not static but rather dependent on the input dynamics. Therefore, Msn2 and Msn4 enable a time-based mode of combinatorial gene regulation that might be applicable to homologous transcription factors in other organisms.

Article and author information

Author details

  1. Zohreh AkhavanAghdam

    Section of Molecular Biology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Joydeb Sinha

    Section of Molecular Biology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Omar P Tabbaa

    Section of Molecular Biology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Nan Hao

    Section of Molecular Biology, University of California, San Diego, La Jolla, United States
    For correspondence
    nhao@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2857-4789

Funding

National Institutes of Health (R01 GM111458)

  • Nan Hao

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Hana El-Samad, University of California, San Francisco, United States

Publication history

  1. Received: June 3, 2016
  2. Accepted: September 12, 2016
  3. Accepted Manuscript published: September 30, 2016 (version 1)
  4. Version of Record published: October 3, 2016 (version 2)

Copyright

© 2016, AkhavanAghdam et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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