Local genetic context shapes the function of a gene regulatory network

Abstract
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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

1. Nagy-Staron AA
(2020) Sequences of gene regulatory network permutations for the article "Local genetic context shapes the function of a gene regulatory network
IST Research Depository, doi:10.15479/AT:ISTA:8951.

https://research-explorer.app.ist.ac.at/record/8951

Article and author information

Author details

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.

"This ORCID iD identifies the author of this article:" 0000-0002-1391-8377
Kathrin Tomasek

Department of Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3768-877X
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.

"This ORCID iD identifies the author of this article:" 0000-0002-0475-856X
Elisabeth Sonnleitner

Department of Microbiology, Immunobiology and Genetics, University of Vienna, Vienna, Austria

Competing interests
The authors declare that no competing interests exist.
Bor Kavčič

Department of Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6041-254X
Tiago Paixão

Quantitative Biology Unit, Instituto Gulbenkian de Ciência, Oeiras, Portugal

Competing interests
The authors declare that no competing interests exist.
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.

"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

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.