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

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.

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.

Download links

Share this article

https://doi.org/10.7554/eLife.65993

Further reading

    1. Chromosomes and Gene Expression
    Shihui Chen, Carolyn Marie Phillips
    Research Article

    RNA interference (RNAi) is a conserved pathway that utilizes Argonaute proteins and their associated small RNAs to exert gene regulatory function on complementary transcripts. While the majority of germline-expressed RNAi proteins reside in perinuclear germ granules, it is unknown whether and how RNAi pathways are spatially organized in other cell types. Here, we find that the small RNA biogenesis machinery is spatially and temporally organized during Caenorhabditis elegans embryogenesis. Specifically, the RNAi factor, SIMR-1, forms visible concentrates during mid-embryogenesis that contain an RNA-dependent RNA polymerase, a poly-UG polymerase, and the unloaded nuclear Argonaute protein, NRDE-3. Curiously, coincident with the appearance of the SIMR granules, the small RNAs bound to NRDE-3 switch from predominantly CSR-class 22G-RNAs to ERGO-dependent 22G-RNAs. NRDE-3 binds ERGO-dependent 22G-RNAs in the somatic cells of larvae and adults to silence ERGO-target genes; here we further demonstrate that NRDE-3-bound, CSR-class 22G-RNAs repress transcription in oocytes. Thus, our study defines two separable roles for NRDE-3, targeting germline-expressed genes during oogenesis to promote global transcriptional repression, and switching during embryogenesis to repress recently duplicated genes and retrotransposons in somatic cells, highlighting the plasticity of Argonaute proteins and the need for more precise temporal characterization of Argonaute-small RNA interactions.

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    Steven Henikoff, David L Levens
    Insight

    A new method for mapping torsion provides insights into the ways that the genome responds to the torsion generated by RNA polymerase II.