1. Chromosomes and Gene Expression
  2. Computational and Systems Biology
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Local genetic context shapes the function of a gene regulatory network

  1. Anna Nagy-Staron  Is a corresponding author
  2. Kathrin Tomasek
  3. Caroline Caruso Carter
  4. Elisabeth Sonnleitner
  5. Bor Kavčič
  6. Tiago Paixão
  7. Calin C Guet  Is a corresponding author
  1. Institute of Science and Technology Austria, Austria
  2. University of Vienna, Austria
  3. Instituto Gulbenkian de Ciência, Portugal
Research Article
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Cite this article as: eLife 2021;10:e65993 doi: 10.7554/eLife.65993

Abstract

Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions, such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks remains a major challenge. Here, we use a well-defined synthetic gene regulatory network to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one gene regulatory network with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual transcriptional units, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of gene regulatory networks.

Data availability

Plasmid sequences are provided in IST Research Depository, DOI 10.15479/AT:ISTA:8951

The following data sets were generated

Article and author information

Author details

  1. Anna Nagy-Staron

    Department of Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria
    For correspondence
    anna.staron@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1391-8377
  2. Kathrin Tomasek

    Department of Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3768-877X
  3. Caroline Caruso Carter

    Department of Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0475-856X
  4. Elisabeth Sonnleitner

    Department of Microbiology, Immunobiology and Genetics, University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  5. Bor Kavčič

    Department of Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6041-254X
  6. Tiago Paixão

    Quantitative Biology Unit, Instituto Gulbenkian de Ciência, Oeiras, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  7. Calin C Guet

    Biology, Institute of Science and Technology Austria, Klosterneuburg, Austria
    For correspondence
    calin@ist.ac.at
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6220-2052

Funding

FP7 People: Marie-Curie Actions (628377)

  • Anna Nagy-Staron

ANR-FWF

  • Calin C Guet

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

Reviewing Editor

  1. Paul B Rainey, Max Planck Institute for Evolutionary Biology, Germany

Publication history

  1. Received: December 21, 2020
  2. Accepted: February 19, 2021
  3. Accepted Manuscript published: March 8, 2021 (version 1)
  4. Version of Record published: March 17, 2021 (version 2)
  5. Version of Record updated: April 26, 2021 (version 3)

Copyright

© 2021, Nagy-Staron 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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