---
_id: '9283'
abstract:
- lang: eng
  text: 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 (GRNs) remains a major challenge. Here, we use a well-defined synthetic
    GRN 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 GRN 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 (TU) within two separate regulons
    without the need for complex regulatory sequences. We propose that relative order
    of individual TUs, with its potential for combinatorial complexity, plays an important
    role in shaping phenotypes of GRNs.
acknowledgement: "We thank J Bollback, L Hurst, M Lagator, C Nizak, O Rivoire, M Savageau,
  G Tkacik, and B Vicozo\r\nfor helpful discussions; A Dolinar and A Greshnova for
  technical assistance; T Bollenbach for supplying the strain JW0336; C Rusnac, and
  members of the Guet lab for comments. The research leading to these results has
  received funding from the People Programme (Marie Curie Actions) of the European
  Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n˚\r\n628377
  (ANS) and an Austrian Science Fund (FWF) grant n˚ I 3901-B32 (CCG)."
article_number: e65993
article_processing_charge: Yes
article_type: original
author:
- first_name: Anna A
  full_name: Nagy-Staron, Anna A
  id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87
  last_name: Nagy-Staron
  orcid: 0000-0002-1391-8377
- first_name: Kathrin
  full_name: Tomasek, Kathrin
  id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
  last_name: Tomasek
  orcid: 0000-0003-3768-877X
- first_name: Caroline
  full_name: Caruso Carter, Caroline
  last_name: Caruso Carter
- first_name: Elisabeth
  full_name: Sonnleitner, Elisabeth
  last_name: Sonnleitner
- first_name: Bor
  full_name: Kavcic, Bor
  id: 350F91D2-F248-11E8-B48F-1D18A9856A87
  last_name: Kavcic
  orcid: 0000-0001-6041-254X
- first_name: Tiago
  full_name: Paixão, Tiago
  last_name: Paixão
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
citation:
  ama: Nagy-Staron AA, Tomasek K, Caruso Carter C, et al. Local genetic context shapes
    the function of a gene regulatory network. <i>eLife</i>. 2021;10. doi:<a href="https://doi.org/10.7554/elife.65993">10.7554/elife.65993</a>
  apa: Nagy-Staron, A. A., Tomasek, K., Caruso Carter, C., Sonnleitner, E., Kavcic,
    B., Paixão, T., &#38; Guet, C. C. (2021). Local genetic context shapes the function
    of a gene regulatory network. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/elife.65993">https://doi.org/10.7554/elife.65993</a>
  chicago: Nagy-Staron, Anna A, Kathrin Tomasek, Caroline Caruso Carter, Elisabeth
    Sonnleitner, Bor Kavcic, Tiago Paixão, and Calin C Guet. “Local Genetic Context
    Shapes the Function of a Gene Regulatory Network.” <i>ELife</i>. eLife Sciences
    Publications, 2021. <a href="https://doi.org/10.7554/elife.65993">https://doi.org/10.7554/elife.65993</a>.
  ieee: A. A. Nagy-Staron <i>et al.</i>, “Local genetic context shapes the function
    of a gene regulatory network,” <i>eLife</i>, vol. 10. eLife Sciences Publications,
    2021.
  ista: Nagy-Staron AA, Tomasek K, Caruso Carter C, Sonnleitner E, Kavcic B, Paixão
    T, Guet CC. 2021. Local genetic context shapes the function of a gene regulatory
    network. eLife. 10, e65993.
  mla: Nagy-Staron, Anna A., et al. “Local Genetic Context Shapes the Function of
    a Gene Regulatory Network.” <i>ELife</i>, vol. 10, e65993, eLife Sciences Publications,
    2021, doi:<a href="https://doi.org/10.7554/elife.65993">10.7554/elife.65993</a>.
  short: A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic,
    T. Paixão, C.C. Guet, ELife 10 (2021).
corr_author: '1'
date_created: 2021-03-23T10:11:46Z
date_published: 2021-03-08T00:00:00Z
date_updated: 2025-06-12T06:36:17Z
day: '08'
ddc:
- '570'
department:
- _id: GaTk
- _id: CaGu
doi: 10.7554/elife.65993
ec_funded: 1
external_id:
  isi:
  - '000631050900001'
  pmid:
  - '33683203'
file:
- access_level: open_access
  checksum: 3c2f44058c2dd45a5a1027f09d263f8e
  content_type: application/pdf
  creator: bkavcic
  date_created: 2021-03-23T10:12:58Z
  date_updated: 2021-03-23T10:12:58Z
  file_id: '9284'
  file_name: elife-65993-v2.pdf
  file_size: 1390469
  relation: main_file
  success: 1
file_date_updated: 2021-03-23T10:12:58Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
keyword:
- Genetics and Molecular Biology
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2517526A-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '628377'
  name: 'The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic
    Networks to Genomic Studies'
- _id: 268BFA92-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03901
  name: Cybergenetic circuits to test composability of gene networks
publication: eLife
publication_identifier:
  issn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
  record:
  - id: '8951'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: Local genetic context shapes the function of a gene regulatory network
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 10
year: '2021'
...