---
_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. eLife. 2021;10. doi:10.7554/elife.65993
apa: Nagy-Staron, A. A., Tomasek, K., Caruso Carter, C., Sonnleitner, E., Kavcic,
B., Paixão, T., & Guet, C. C. (2021). Local genetic context shapes the function
of a gene regulatory network. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.65993
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.” ELife. eLife Sciences
Publications, 2021. https://doi.org/10.7554/elife.65993.
ieee: A. A. Nagy-Staron et al., “Local genetic context shapes the function
of a gene regulatory network,” eLife, 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.” ELife, vol. 10, e65993, eLife Sciences Publications,
2021, doi:10.7554/elife.65993.
short: A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic,
T. Paixão, C.C. Guet, ELife 10 (2021).
date_created: 2021-03-23T10:11:46Z
date_published: 2021-03-08T00:00:00Z
date_updated: 2024-02-21T12:41:57Z
day: '08'
ddc:
- '570'
department:
- _id: GaTk
- _id: CaGu
doi: 10.7554/elife.65993
ec_funded: 1
external_id:
isi:
- '000631050900001'
file:
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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
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has_accepted_license: '1'
intvolume: ' 10'
isi: 1
keyword:
- Genetics and Molecular Biology
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
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: 'CyberCircuits: 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:
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relation: research_data
status: public
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2021'
...
---
_id: '8951'
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 remains a major challenge. Here, we use a well-defined synthetic gene
regulatory network to study 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. Our results demonstrate that changes
in local genetic context can place a single 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.
article_processing_charge: No
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
citation:
ama: Nagy-Staron AA. Sequences of gene regulatory network permutations for the article
“Local genetic context shapes the function of a gene regulatory network.” 2020.
doi:10.15479/AT:ISTA:8951
apa: Nagy-Staron, A. A. (2020). Sequences of gene regulatory network permutations
for the article “Local genetic context shapes the function of a gene regulatory
network.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8951
chicago: Nagy-Staron, Anna A. “Sequences of Gene Regulatory Network Permutations
for the Article ‘Local Genetic Context Shapes the Function of a Gene Regulatory
Network.’” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8951.
ieee: A. A. Nagy-Staron, “Sequences of gene regulatory network permutations for
the article ‘Local genetic context shapes the function of a gene regulatory network.’”
Institute of Science and Technology Austria, 2020.
ista: Nagy-Staron AA. 2020. Sequences of gene regulatory network permutations for
the article ‘Local genetic context shapes the function of a gene regulatory network’,
Institute of Science and Technology Austria, 10.15479/AT:ISTA:8951.
mla: Nagy-Staron, Anna A. Sequences of Gene Regulatory Network Permutations for
the Article “Local Genetic Context Shapes the Function of a Gene Regulatory Network.”
Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8951.
short: A.A. Nagy-Staron, (2020).
contributor:
- contributor_type: project_member
first_name: Anna A
id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87
last_name: Nagy-Staron
- contributor_type: project_member
first_name: Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
- contributor_type: project_member
first_name: Caroline
last_name: Caruso Carter
- contributor_type: project_member
first_name: Elisabeth
last_name: Sonnleitner
- contributor_type: project_member
first_name: Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- contributor_type: project_member
first_name: Tiago
last_name: Paixão
- contributor_type: project_manager
first_name: Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
date_created: 2020-12-20T10:00:26Z
date_published: 2020-12-21T00:00:00Z
date_updated: 2024-02-21T12:41:57Z
day: '21'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:8951
file:
- access_level: open_access
checksum: f57862aeee1690c7effd2b1117d40ed1
content_type: text/plain
creator: bkavcic
date_created: 2020-12-20T09:52:52Z
date_updated: 2020-12-20T09:52:52Z
file_id: '8952'
file_name: readme.txt
file_size: 523
relation: main_file
success: 1
- access_level: open_access
checksum: f2c6d5232ec6d551b6993991e8689e9f
content_type: application/octet-stream
creator: bkavcic
date_created: 2020-12-20T22:01:44Z
date_updated: 2020-12-20T22:01:44Z
file_id: '8954'
file_name: GRNs Research depository.gb
file_size: 379228
relation: main_file
success: 1
file_date_updated: 2020-12-20T22:01:44Z
has_accepted_license: '1'
keyword:
- Gene regulatory networks
- Gene expression
- Escherichia coli
- Synthetic Biology
month: '12'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '9283'
relation: used_in_publication
status: public
status: public
title: Sequences of gene regulatory network permutations for the article "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: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '1084'
abstract:
- lang: eng
text: 'BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis
controlling the response to antimicrobial peptides. In the presence of extracellular
bacitracin and nisin, respectively, the two response regulators (RRs) bind their
target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target
gene expression and ultimately antibiotic resistance. Despite high sequence similarity
between the RRs BceR and PsdR and their known binding sites, no cross-regulation
has been observed between them. We therefore investigated the specificity determinants
of PbceA and PpsdA that ensure the insulation of these two paralogous pathways
at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the
regulatory regions within these two promoters contain three important elements:
in addition to the known (main) binding site, we identified a linker region and
a secondary binding site that are crucial for functionality. Initial binding to
the high-affinity, low-specificity main binding site is a prerequisite for the
subsequent highly specific binding of a second RR dimer to the low-affinity secondary
binding site. In addition to this hierarchical cooperative binding, discrimination
requires a competition of the two RRs for their respective binding site mediated
by only slight differences in binding affinities.'
article_processing_charge: No
author:
- first_name: Chong
full_name: Fang, Chong
last_name: Fang
- 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: Martin
full_name: Grafe, Martin
last_name: Grafe
- first_name: Ralf
full_name: Heermann, Ralf
last_name: Heermann
- first_name: Kirsten
full_name: Jung, Kirsten
last_name: Jung
- first_name: Susanne
full_name: Gebhard, Susanne
last_name: Gebhard
- first_name: Thorsten
full_name: Mascher, Thorsten
last_name: Mascher
citation:
ama: Fang C, Nagy-Staron AA, Grafe M, et al. Insulation and wiring specificity of
BceR like response regulators and their target promoters in Bacillus subtilis.
Molecular Microbiology. 2017;104(1):16-31. doi:10.1111/mmi.13597
apa: Fang, C., Nagy-Staron, A. A., Grafe, M., Heermann, R., Jung, K., Gebhard, S.,
& Mascher, T. (2017). Insulation and wiring specificity of BceR like response
regulators and their target promoters in Bacillus subtilis. Molecular Microbiology.
Wiley-Blackwell. https://doi.org/10.1111/mmi.13597
chicago: Fang, Chong, Anna A Nagy-Staron, Martin Grafe, Ralf Heermann, Kirsten Jung,
Susanne Gebhard, and Thorsten Mascher. “Insulation and Wiring Specificity of BceR
like Response Regulators and Their Target Promoters in Bacillus Subtilis.” Molecular
Microbiology. Wiley-Blackwell, 2017. https://doi.org/10.1111/mmi.13597.
ieee: C. Fang et al., “Insulation and wiring specificity of BceR like response
regulators and their target promoters in Bacillus subtilis,” Molecular Microbiology,
vol. 104, no. 1. Wiley-Blackwell, pp. 16–31, 2017.
ista: Fang C, Nagy-Staron AA, Grafe M, Heermann R, Jung K, Gebhard S, Mascher T.
2017. Insulation and wiring specificity of BceR like response regulators and their
target promoters in Bacillus subtilis. Molecular Microbiology. 104(1), 16–31.
mla: Fang, Chong, et al. “Insulation and Wiring Specificity of BceR like Response
Regulators and Their Target Promoters in Bacillus Subtilis.” Molecular Microbiology,
vol. 104, no. 1, Wiley-Blackwell, 2017, pp. 16–31, doi:10.1111/mmi.13597.
short: C. Fang, A.A. Nagy-Staron, M. Grafe, R. Heermann, K. Jung, S. Gebhard, T.
Mascher, Molecular Microbiology 104 (2017) 16–31.
date_created: 2018-12-11T11:50:03Z
date_published: 2017-04-01T00:00:00Z
date_updated: 2023-09-20T11:48:43Z
day: '01'
department:
- _id: CaGu
doi: 10.1111/mmi.13597
external_id:
isi:
- '000398059200002'
intvolume: ' 104'
isi: 1
issue: '1'
language:
- iso: eng
month: '04'
oa_version: None
page: 16 - 31
publication: Molecular Microbiology
publication_identifier:
issn:
- ' 0950382X'
publication_status: published
publisher: Wiley-Blackwell
publist_id: '6294'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Insulation and wiring specificity of BceR like response regulators and their
target promoters in Bacillus subtilis
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 104
year: '2017'
...
---
_id: '1894'
abstract:
- lang: eng
text: 'Background: Bacterial Dsb enzymes are involved in the oxidative folding of
many proteins, through the formation of disulfide bonds between their cysteine
residues. The Dsb protein network has been well characterized in cells of the
model microorganism Escherichia coli. To gain insight into the functioning of
the Dsb system in epsilon-Proteobacteria, where it plays an important role in
the colonization process, we studied two homologs of the main Escherichia coli
Dsb oxidase (EcDsbA) that are present in the cells of the enteric pathogen Campylobacter
jejuni, the most frequently reported bacterial cause of human enteritis in the
world. Methods and Results: Phylogenetic analysis suggests the horizontal transfer
of the epsilon-Proteobacterial DsbAs from a common ancestor to gamma-Proteobacteria,
which then gave rise to the DsbL lineage. Phenotype and enzymatic assays suggest
that the two C. jejuni DsbAs play different roles in bacterial cells and have
divergent substrate spectra. CjDsbA1 is essential for the motility and autoagglutination
phenotypes, while CjDsbA2 has no impact on those processes. CjDsbA1 plays a critical
role in the oxidative folding that ensures the activity of alkaline phosphatase
CjPhoX, whereas CjDsbA2 is crucial for the activity of arylsulfotransferase CjAstA,
encoded within the dsbA2-dsbB-astA operon. Conclusions: Our results show that
CjDsbA1 is the primary thiol-oxidoreductase affecting life processes associated
with bacterial spread and host colonization, as well as ensuring the oxidative
folding of particular protein substrates. In contrast, CjDsbA2 activity does not
affect the same processes and so far its oxidative folding activity has been demonstrated
for one substrate, arylsulfotransferase CjAstA. The results suggest the cooperation
between CjDsbA2 and CjDsbB. In the case of the CjDsbA1, this cooperation is not
exclusive and there is probably another protein to be identified in C. jejuni
cells that acts to re-oxidize CjDsbA1. Altogether the data presented here constitute
the considerable insight to the Epsilonproteobacterial Dsb systems, which have
been poorly understood so far.'
article_number: e106247
author:
- first_name: Anna
full_name: Grabowska, Anna
last_name: Grabowska
- first_name: Ewa
full_name: Wywiał, Ewa
last_name: Wywiał
- first_name: Stanislaw
full_name: Dunin Horkawicz, Stanislaw
last_name: Dunin Horkawicz
- first_name: Anna
full_name: Łasica, Anna
last_name: Łasica
- first_name: Marc
full_name: Wösten, Marc
last_name: Wösten
- first_name: Anna A
full_name: Nagy-Staron, Anna A
id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87
last_name: Nagy-Staron
- first_name: Renata
full_name: Godlewska, Renata
last_name: Godlewska
- first_name: Katarzyna
full_name: Bocian Ostrzycka, Katarzyna
last_name: Bocian Ostrzycka
- first_name: Katarzyna
full_name: Pieńkowska, Katarzyna
last_name: Pieńkowska
- first_name: Paweł
full_name: Łaniewski, Paweł
last_name: Łaniewski
- first_name: Janusz
full_name: Bujnicki, Janusz
last_name: Bujnicki
- first_name: Jos
full_name: Van Putten, Jos
last_name: Van Putten
- first_name: Elzbieta
full_name: Jagusztyn Krynicka, Elzbieta
last_name: Jagusztyn Krynicka
citation:
ama: Grabowska A, Wywiał E, Dunin Horkawicz S, et al. Functional and bioinformatics
analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase,
DsbA. PLoS One. 2014;9(9). doi:10.1371/journal.pone.0106247
apa: Grabowska, A., Wywiał, E., Dunin Horkawicz, S., Łasica, A., Wösten, M., Nagy-Staron,
A. A., … Jagusztyn Krynicka, E. (2014). Functional and bioinformatics analysis
of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA.
PLoS One. Public Library of Science. https://doi.org/10.1371/journal.pone.0106247
chicago: Grabowska, Anna, Ewa Wywiał, Stanislaw Dunin Horkawicz, Anna Łasica, Marc
Wösten, Anna A Nagy-Staron, Renata Godlewska, et al. “Functional and Bioinformatics
Analysis of Two Campylobacter Jejuni Homologs of the Thiol-Disulfide Oxidoreductase,
DsbA.” PLoS One. Public Library of Science, 2014. https://doi.org/10.1371/journal.pone.0106247.
ieee: A. Grabowska et al., “Functional and bioinformatics analysis of two
Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA,” PLoS
One, vol. 9, no. 9. Public Library of Science, 2014.
ista: Grabowska A, Wywiał E, Dunin Horkawicz S, Łasica A, Wösten M, Nagy-Staron
AA, Godlewska R, Bocian Ostrzycka K, Pieńkowska K, Łaniewski P, Bujnicki J, Van
Putten J, Jagusztyn Krynicka E. 2014. Functional and bioinformatics analysis of
two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA.
PLoS One. 9(9), e106247.
mla: Grabowska, Anna, et al. “Functional and Bioinformatics Analysis of Two Campylobacter
Jejuni Homologs of the Thiol-Disulfide Oxidoreductase, DsbA.” PLoS One,
vol. 9, no. 9, e106247, Public Library of Science, 2014, doi:10.1371/journal.pone.0106247.
short: A. Grabowska, E. Wywiał, S. Dunin Horkawicz, A. Łasica, M. Wösten, A.A. Nagy-Staron,
R. Godlewska, K. Bocian Ostrzycka, K. Pieńkowska, P. Łaniewski, J. Bujnicki, J.
Van Putten, E. Jagusztyn Krynicka, PLoS One 9 (2014).
date_created: 2018-12-11T11:54:35Z
date_published: 2014-09-02T00:00:00Z
date_updated: 2021-01-12T06:53:54Z
day: '02'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1371/journal.pone.0106247
file:
- access_level: open_access
checksum: 7d02c3da7f72b82bb5d7932d80c3251f
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:16:19Z
date_updated: 2020-07-14T12:45:20Z
file_id: '5205'
file_name: IST-2016-438-v1+1_journal.pone.0106247.pdf
file_size: 4248801
relation: main_file
file_date_updated: 2020-07-14T12:45:20Z
has_accepted_license: '1'
intvolume: ' 9'
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: PLoS One
publication_status: published
publisher: Public Library of Science
publist_id: '5201'
pubrep_id: '438'
quality_controlled: '1'
scopus_import: 1
status: public
title: Functional and bioinformatics analysis of two Campylobacter jejuni homologs
of the thiol-disulfide oxidoreductase, DsbA
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: 4435EBFC-F248-11E8-B48F-1D18A9856A87
volume: 9
year: '2014'
...