--- _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: - 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 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: record: - id: '8951' 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' ...