[{"project":[{"call_identifier":"FP7","_id":"2517526A-B435-11E9-9278-68D0E5697425","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","name":"CyberCircuits: Cybergenetic circuits to test composability of gene networks","grant_number":"I03901"}],"article_number":"e65993","external_id":{"isi":["000631050900001"]},"article_processing_charge":"Yes","author":[{"id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","first_name":"Anna A","full_name":"Nagy-Staron, Anna A","orcid":"0000-0002-1391-8377","last_name":"Nagy-Staron"},{"id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","first_name":"Kathrin","full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X","last_name":"Tomasek"},{"full_name":"Caruso Carter, Caroline","last_name":"Caruso Carter","first_name":"Caroline"},{"last_name":"Sonnleitner","full_name":"Sonnleitner, Elisabeth","first_name":"Elisabeth"},{"last_name":"Kavcic","orcid":"0000-0001-6041-254X","full_name":"Kavcic, Bor","first_name":"Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Tiago","last_name":"Paixão","full_name":"Paixão, Tiago"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"}],"title":"Local genetic context shapes the function of a gene regulatory network","citation":{"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.","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.","short":"A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic, T. Paixão, C.C. Guet, ELife 10 (2021).","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","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","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"quality_controlled":"1","publisher":"eLife Sciences Publications","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).","date_created":"2021-03-23T10:11:46Z","date_published":"2021-03-08T00:00:00Z","doi":"10.7554/elife.65993","year":"2021","has_accepted_license":"1","isi":1,"publication":"eLife","day":"08","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","keyword":["Genetics and Molecular Biology"],"status":"public","_id":"9283","file_date_updated":"2021-03-23T10:12:58Z","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"date_updated":"2024-02-21T12:41:57Z","ddc":["570"],"intvolume":" 10","month":"03","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."}],"oa_version":"Published Version","ec_funded":1,"volume":10,"related_material":{"record":[{"status":"public","id":"8951","relation":"research_data"}]},"publication_status":"published","publication_identifier":{"issn":["2050-084X"]},"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"checksum":"3c2f44058c2dd45a5a1027f09d263f8e","file_id":"9284","file_size":1390469,"date_updated":"2021-03-23T10:12:58Z","creator":"bkavcic","file_name":"elife-65993-v2.pdf","date_created":"2021-03-23T10:12:58Z"}]},{"status":"public","keyword":["Gene regulatory networks","Gene expression","Escherichia coli","Synthetic Biology"],"type":"research_data","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"8951","file_date_updated":"2020-12-20T22:01:44Z","department":[{"_id":"CaGu"}],"title":"Sequences of gene regulatory network permutations for the article \"Local genetic context shapes the function of a gene regulatory network\"","author":[{"id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","first_name":"Anna A","last_name":"Nagy-Staron","orcid":"0000-0002-1391-8377","full_name":"Nagy-Staron, Anna A"}],"article_processing_charge":"No","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2024-02-21T12:41:57Z","citation":{"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.","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.","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","short":"A.A. Nagy-Staron, (2020).","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.","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."},"month":"12","publisher":"Institute of Science and Technology Austria","oa":1,"oa_version":"Published Version","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."}],"doi":"10.15479/AT:ISTA:8951","related_material":{"record":[{"relation":"used_in_publication","id":"9283","status":"public"}]},"date_published":"2020-12-21T00:00:00Z","date_created":"2020-12-20T10:00:26Z","contributor":[{"id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","contributor_type":"project_member","first_name":"Anna A","last_name":"Nagy-Staron"},{"contributor_type":"project_member","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","first_name":"Kathrin","last_name":"Tomasek"},{"last_name":"Caruso Carter","first_name":"Caroline","contributor_type":"project_member"},{"first_name":"Elisabeth","contributor_type":"project_member","last_name":"Sonnleitner"},{"last_name":"Kavcic","orcid":"0000-0001-6041-254X","first_name":"Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","contributor_type":"project_member"},{"last_name":"Paixão","first_name":"Tiago","contributor_type":"project_member"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","contributor_type":"project_manager","last_name":"Guet","orcid":"0000-0001-6220-2052"}],"file":[{"creator":"bkavcic","file_size":523,"date_updated":"2020-12-20T09:52:52Z","file_name":"readme.txt","date_created":"2020-12-20T09:52:52Z","relation":"main_file","access_level":"open_access","content_type":"text/plain","success":1,"file_id":"8952","checksum":"f57862aeee1690c7effd2b1117d40ed1"},{"date_created":"2020-12-20T22:01:44Z","file_name":"GRNs Research depository.gb","creator":"bkavcic","date_updated":"2020-12-20T22:01:44Z","file_size":379228,"file_id":"8954","checksum":"f2c6d5232ec6d551b6993991e8689e9f","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/octet-stream"}],"day":"21","has_accepted_license":"1","year":"2020"},{"publisher":"Wiley-Blackwell","quality_controlled":"1","publication":"Molecular Microbiology","day":"01","year":"2017","isi":1,"date_created":"2018-12-11T11:50:03Z","date_published":"2017-04-01T00:00:00Z","doi":"10.1111/mmi.13597","page":"16 - 31","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","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","short":"C. Fang, A.A. Nagy-Staron, M. Grafe, R. Heermann, K. Jung, S. Gebhard, T. Mascher, Molecular Microbiology 104 (2017) 16–31.","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.","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.","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.","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."},"title":"Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis","article_processing_charge":"No","external_id":{"isi":["000398059200002"]},"author":[{"first_name":"Chong","last_name":"Fang","full_name":"Fang, Chong"},{"full_name":"Nagy-Staron, Anna A","orcid":"0000-0002-1391-8377","last_name":"Nagy-Staron","first_name":"Anna A","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Martin","full_name":"Grafe, Martin","last_name":"Grafe"},{"last_name":"Heermann","full_name":"Heermann, Ralf","first_name":"Ralf"},{"full_name":"Jung, Kirsten","last_name":"Jung","first_name":"Kirsten"},{"first_name":"Susanne","last_name":"Gebhard","full_name":"Gebhard, Susanne"},{"first_name":"Thorsten","last_name":"Mascher","full_name":"Mascher, Thorsten"}],"publist_id":"6294","oa_version":"None","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."}],"intvolume":" 104","month":"04","scopus_import":"1","language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"issn":[" 0950382X"]},"volume":104,"issue":"1","_id":"1084","status":"public","type":"journal_article","date_updated":"2023-09-20T11:48:43Z","department":[{"_id":"CaGu"}]},{"issue":"9","volume":9,"file":[{"file_name":"IST-2016-438-v1+1_journal.pone.0106247.pdf","date_created":"2018-12-12T10:16:19Z","file_size":4248801,"date_updated":"2020-07-14T12:45:20Z","creator":"system","checksum":"7d02c3da7f72b82bb5d7932d80c3251f","file_id":"5205","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"language":[{"iso":"eng"}],"publication_status":"published","month":"09","intvolume":" 9","scopus_import":1,"oa_version":"Published Version","abstract":[{"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.","lang":"eng"}],"file_date_updated":"2020-07-14T12:45:20Z","department":[{"_id":"CaGu"}],"ddc":["570"],"date_updated":"2021-01-12T06:53:54Z","status":"public","pubrep_id":"438","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"1894","date_published":"2014-09-02T00:00:00Z","doi":"10.1371/journal.pone.0106247","date_created":"2018-12-11T11:54:35Z","day":"02","publication":"PLoS One","has_accepted_license":"1","year":"2014","publisher":"Public Library of Science","quality_controlled":"1","oa":1,"title":"Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA","publist_id":"5201","author":[{"first_name":"Anna","full_name":"Grabowska, Anna","last_name":"Grabowska"},{"first_name":"Ewa","full_name":"Wywiał, Ewa","last_name":"Wywiał"},{"last_name":"Dunin Horkawicz","full_name":"Dunin Horkawicz, Stanislaw","first_name":"Stanislaw"},{"first_name":"Anna","last_name":"Łasica","full_name":"Łasica, Anna"},{"full_name":"Wösten, Marc","last_name":"Wösten","first_name":"Marc"},{"first_name":"Anna A","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","last_name":"Nagy-Staron","full_name":"Nagy-Staron, Anna A"},{"full_name":"Godlewska, Renata","last_name":"Godlewska","first_name":"Renata"},{"first_name":"Katarzyna","last_name":"Bocian Ostrzycka","full_name":"Bocian Ostrzycka, Katarzyna"},{"full_name":"Pieńkowska, Katarzyna","last_name":"Pieńkowska","first_name":"Katarzyna"},{"first_name":"Paweł","full_name":"Łaniewski, Paweł","last_name":"Łaniewski"},{"full_name":"Bujnicki, Janusz","last_name":"Bujnicki","first_name":"Janusz"},{"first_name":"Jos","full_name":"Van Putten, Jos","last_name":"Van Putten"},{"full_name":"Jagusztyn Krynicka, Elzbieta","last_name":"Jagusztyn Krynicka","first_name":"Elzbieta"}],"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","citation":{"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.","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).","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","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","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.","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.","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."},"article_number":"e106247"}]