[{"acknowledgement":"Tatjana Petrov’s research was supported in part by SNSF Advanced Postdoctoral Mobility Fellowship grant number P300P2 161067, the Ministry of Science, Research and the Arts of the state of Baden-Wurttemberg, and the DFG Centre of Excellence 2117 ‘Centre for the Advanced Study of Collective Behaviour’ (ID: 422037984). Claudia Igler is the recipient of a DOC Fellowship of the Austrian Academy of Sciences. Thomas A. Henzinger’s research was supported in part by the Austrian Science Fund (FWF) under grant Z211-N23 (Wittgenstein Award).","oa":1,"publisher":"Elsevier","quality_controlled":"1","publication":"Theoretical Computer Science","day":"04","year":"2021","has_accepted_license":"1","isi":1,"date_created":"2021-07-11T22:01:18Z","doi":"10.1016/j.tcs.2021.05.023","date_published":"2021-06-04T00:00:00Z","page":"1-16","project":[{"call_identifier":"FWF","_id":"25F42A32-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","grant_number":"Z211"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"mla":"Petrov, Tatjana, et al. “Long Lived Transients in Gene Regulation.” Theoretical Computer Science, vol. 893, Elsevier, 2021, pp. 1–16, doi:10.1016/j.tcs.2021.05.023.","ama":"Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. Long lived transients in gene regulation. Theoretical Computer Science. 2021;893:1-16. doi:10.1016/j.tcs.2021.05.023","apa":"Petrov, T., Igler, C., Sezgin, A., Henzinger, T. A., & Guet, C. C. (2021). Long lived transients in gene regulation. Theoretical Computer Science. Elsevier. https://doi.org/10.1016/j.tcs.2021.05.023","ieee":"T. Petrov, C. Igler, A. Sezgin, T. A. Henzinger, and C. C. Guet, “Long lived transients in gene regulation,” Theoretical Computer Science, vol. 893. Elsevier, pp. 1–16, 2021.","short":"T. Petrov, C. Igler, A. Sezgin, T.A. Henzinger, C.C. Guet, Theoretical Computer Science 893 (2021) 1–16.","chicago":"Petrov, Tatjana, Claudia Igler, Ali Sezgin, Thomas A Henzinger, and Calin C Guet. “Long Lived Transients in Gene Regulation.” Theoretical Computer Science. Elsevier, 2021. https://doi.org/10.1016/j.tcs.2021.05.023.","ista":"Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. 2021. Long lived transients in gene regulation. Theoretical Computer Science. 893, 1–16."},"title":"Long lived transients in gene regulation","external_id":{"isi":["000710180500002"]},"article_processing_charge":"No","author":[{"first_name":"Tatjana","last_name":"Petrov","full_name":"Petrov, Tatjana"},{"id":"46613666-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia","last_name":"Igler","full_name":"Igler, Claudia"},{"full_name":"Sezgin, Ali","last_name":"Sezgin","first_name":"Ali","id":"4C7638DA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Henzinger, Thomas A","orcid":"0000-0002-2985-7724","last_name":"Henzinger","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas A"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"}],"oa_version":"Published Version","abstract":[{"text":"Gene expression is regulated by the set of transcription factors (TFs) that bind to the promoter. The ensuing regulating function is often represented as a combinational logic circuit, where output (gene expression) is determined by current input values (promoter bound TFs) only. However, the simultaneous arrival of TFs is a strong assumption, since transcription and translation of genes introduce intrinsic time delays and there is no global synchronisation among the arrival times of different molecular species at their targets. We present an experimentally implementable genetic circuit with two inputs and one output, which in the presence of small delays in input arrival, exhibits qualitatively distinct population-level phenotypes, over timescales that are longer than typical cell doubling times. From a dynamical systems point of view, these phenotypes represent long-lived transients: although they converge to the same value eventually, they do so after a very long time span. The key feature of this toy model genetic circuit is that, despite having only two inputs and one output, it is regulated by twenty-three distinct DNA-TF configurations, two of which are more stable than others (DNA looped states), one promoting and another blocking the expression of the output gene. Small delays in input arrival time result in a majority of cells in the population quickly reaching the stable state associated with the first input, while exiting of this stable state occurs at a slow timescale. In order to mechanistically model the behaviour of this genetic circuit, we used a rule-based modelling language, and implemented a grid-search to find parameter combinations giving rise to long-lived transients. Our analysis shows that in the absence of feedback, there exist path-dependent gene regulatory mechanisms based on the long timescale of transients. The behaviour of this toy model circuit suggests that gene regulatory networks can exploit event timing to create phenotypes, and it opens the possibility that they could use event timing to memorise events, without regulatory feedback. The model reveals the importance of (i) mechanistically modelling the transitions between the different DNA-TF states, and (ii) employing transient analysis thereof.","lang":"eng"}],"intvolume":" 893","month":"06","scopus_import":"1","language":[{"iso":"eng"}],"file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"checksum":"d3aef34cfb13e53bba4cf44d01680793","file_id":"11364","creator":"dernst","file_size":2566504,"date_updated":"2022-05-12T12:13:27Z","file_name":"2021_TheoreticalComputerScience_Petrov.pdf","date_created":"2022-05-12T12:13:27Z"}],"publication_status":"published","publication_identifier":{"issn":["0304-3975"]},"volume":893,"_id":"9647","status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"type":"journal_article","article_type":"original","ddc":["004"],"date_updated":"2023-08-10T14:11:19Z","file_date_updated":"2022-05-12T12:13:27Z","department":[{"_id":"ToHe"},{"_id":"CaGu"}]},{"oa":1,"quality_controlled":"1","publisher":"Frontiers","date_created":"2019-07-28T21:59:18Z","date_published":"2019-06-03T00:00:00Z","doi":"10.3389/fmicb.2019.01171","year":"2019","isi":1,"has_accepted_license":"1","publication":"Frontiers in Microbiology","day":"03","project":[{"_id":"251EE76E-B435-11E9-9278-68D0E5697425","name":"Design principles underlying genetic switch architecture (DOC Fellowship)","grant_number":"24573"}],"article_number":"1171","article_processing_charge":"Yes (via OA deal)","external_id":{"isi":["000470131200001"]},"author":[{"last_name":"Igler","full_name":"Igler, Claudia","first_name":"Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Stephen T.","full_name":"Abedon, Stephen T.","last_name":"Abedon"}],"title":"Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision","citation":{"apa":"Igler, C., & Abedon, S. T. (2019). Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology. Frontiers. https://doi.org/10.3389/fmicb.2019.01171","ama":"Igler C, Abedon ST. Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology. 2019;10. doi:10.3389/fmicb.2019.01171","short":"C. Igler, S.T. Abedon, Frontiers in Microbiology 10 (2019).","ieee":"C. Igler and S. T. Abedon, “Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision,” Frontiers in Microbiology, vol. 10. Frontiers, 2019.","mla":"Igler, Claudia, and Stephen T. Abedon. “Commentary: A Host-Produced Quorum-Sensing Autoinducer Controls a Phage Lysis-Lysogeny Decision.” Frontiers in Microbiology, vol. 10, 1171, Frontiers, 2019, doi:10.3389/fmicb.2019.01171.","ista":"Igler C, Abedon ST. 2019. Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology. 10, 1171.","chicago":"Igler, Claudia, and Stephen T. Abedon. “Commentary: A Host-Produced Quorum-Sensing Autoinducer Controls a Phage Lysis-Lysogeny Decision.” Frontiers in Microbiology. Frontiers, 2019. https://doi.org/10.3389/fmicb.2019.01171."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","scopus_import":"1","intvolume":" 10","month":"06","abstract":[{"lang":"eng","text":"With the recent publication by Silpe and Bassler (2019), considering phage detection of a bacterial quorum-sensing (QS) autoinducer, we now have as many as five examples of phage-associated intercellular communication (Table 1). Each potentially involves ecological inferences by phages as to concentrations of surrounding phage-infected or uninfected bacteria. While the utility of phage detection of bacterial QS molecules may at first glance appear to be straightforward, we suggest in this commentary that the underlying ecological explanation is unlikely to be simple."}],"oa_version":"Published Version","volume":10,"publication_status":"published","language":[{"iso":"eng"}],"file":[{"file_name":"2019_Frontiers_Igler.pdf","date_created":"2019-07-29T07:51:54Z","creator":"apreinsp","file_size":246151,"date_updated":"2020-07-14T12:47:38Z","checksum":"317a06067e9a8e717bb55f23e0d77ba7","file_id":"6722","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"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)"},"type":"journal_article","status":"public","_id":"6717","file_date_updated":"2020-07-14T12:47:38Z","department":[{"_id":"CaGu"}],"date_updated":"2023-08-29T06:41:20Z","ddc":["570"]},{"page":"155-187","date_created":"2019-12-04T16:07:50Z","date_published":"2019-09-17T00:00:00Z","doi":"10.1007/978-3-030-31304-3_9","year":"2019","isi":1,"publication":"17th International Conference on Computational Methods in Systems Biology","day":"17","quality_controlled":"1","publisher":"Springer Nature","external_id":{"isi":["000557875100009"]},"article_processing_charge":"No","author":[{"last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"},{"id":"40876CD8-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas A","last_name":"Henzinger","full_name":"Henzinger, Thomas A","orcid":"0000−0002−2985−7724"},{"first_name":"Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87","full_name":"Igler, Claudia","last_name":"Igler"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","first_name":"Tatjana","orcid":"0000-0002-9041-0905","full_name":"Petrov, Tatjana","last_name":"Petrov"},{"id":"4C7638DA-F248-11E8-B48F-1D18A9856A87","first_name":"Ali","last_name":"Sezgin","full_name":"Sezgin, Ali"}],"title":"Transient memory in gene regulation","citation":{"chicago":"Guet, Calin C, Thomas A Henzinger, Claudia Igler, Tatjana Petrov, and Ali Sezgin. “Transient Memory in Gene Regulation.” In 17th International Conference on Computational Methods in Systems Biology, 11773:155–87. Springer Nature, 2019. https://doi.org/10.1007/978-3-030-31304-3_9.","ista":"Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. 2019. Transient memory in gene regulation. 17th International Conference on Computational Methods in Systems Biology. CMSB: Computational Methods in Systems Biology, LNCS, vol. 11773, 155–187.","mla":"Guet, Calin C., et al. “Transient Memory in Gene Regulation.” 17th International Conference on Computational Methods in Systems Biology, vol. 11773, Springer Nature, 2019, pp. 155–87, doi:10.1007/978-3-030-31304-3_9.","short":"C.C. Guet, T.A. Henzinger, C. Igler, T. Petrov, A. Sezgin, in:, 17th International Conference on Computational Methods in Systems Biology, Springer Nature, 2019, pp. 155–187.","ieee":"C. C. Guet, T. A. Henzinger, C. Igler, T. Petrov, and A. Sezgin, “Transient memory in gene regulation,” in 17th International Conference on Computational Methods in Systems Biology, Trieste, Italy, 2019, vol. 11773, pp. 155–187.","ama":"Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. Transient memory in gene regulation. In: 17th International Conference on Computational Methods in Systems Biology. Vol 11773. Springer Nature; 2019:155-187. doi:10.1007/978-3-030-31304-3_9","apa":"Guet, C. C., Henzinger, T. A., Igler, C., Petrov, T., & Sezgin, A. (2019). Transient memory in gene regulation. In 17th International Conference on Computational Methods in Systems Biology (Vol. 11773, pp. 155–187). Trieste, Italy: Springer Nature. https://doi.org/10.1007/978-3-030-31304-3_9"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","project":[{"name":"The Wittgenstein Prize","grant_number":"Z211","call_identifier":"FWF","_id":"25F42A32-B435-11E9-9278-68D0E5697425"},{"grant_number":"24573","name":"Design principles underlying genetic switch architecture","_id":"251EE76E-B435-11E9-9278-68D0E5697425"}],"volume":11773,"publication_status":"published","publication_identifier":{"issn":["0302-9743"],"isbn":["9783030313036","9783030313043"],"eissn":["1611-3349"]},"language":[{"iso":"eng"}],"alternative_title":["LNCS"],"scopus_import":"1","intvolume":" 11773","month":"09","abstract":[{"lang":"eng","text":"The expression of a gene is characterised by its transcription factors and the function processing them. If the transcription factors are not affected by gene products, the regulating function is often represented as a combinational logic circuit, where the outputs (product) are determined by current input values (transcription factors) only, and are hence independent on their relative arrival times. However, the simultaneous arrival of transcription factors (TFs) in genetic circuits is a strong assumption, given that the processes of transcription and translation of a gene into a protein introduce intrinsic time delays and that there is no global synchronisation among the arrival times of different molecular species at molecular targets.\r\n\r\nIn this paper, we construct an experimentally implementable genetic circuit with two inputs and a single output, such that, in presence of small delays in input arrival, the circuit exhibits qualitatively distinct observable phenotypes. In particular, these phenotypes are long lived transients: they all converge to a single value, but so slowly, that they seem stable for an extended time period, longer than typical experiment duration. We used rule-based language to prototype our circuit, and we implemented a search for finding the parameter combinations raising the phenotypes of interest.\r\n\r\nThe behaviour of our prototype circuit has wide implications. First, it suggests that GRNs can exploit event timing to create phenotypes. Second, it opens the possibility that GRNs are using event timing to react to stimuli and memorise events, without explicit feedback in regulation. From the modelling perspective, our prototype circuit demonstrates the critical importance of analysing the transient dynamics at the promoter binding sites of the DNA, before applying rapid equilibrium assumptions."}],"oa_version":"None","department":[{"_id":"CaGu"},{"_id":"ToHe"}],"date_updated":"2023-09-06T11:18:08Z","conference":{"name":"CMSB: Computational Methods in Systems Biology","location":"Trieste, Italy","end_date":"2019-09-20","start_date":"2019-09-18"},"type":"conference","status":"public","_id":"7147"},{"department":[{"_id":"CaGu"}],"file_date_updated":"2021-02-11T11:17:13Z","supervisor":[{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet"}],"date_updated":"2024-02-21T13:45:52Z","ddc":["576","579"],"type":"dissertation","status":"public","keyword":["gene regulation","biophysics","transcription factor binding","bacteria"],"_id":"6371","related_material":{"record":[{"id":"67","status":"public","relation":"part_of_dissertation"},{"relation":"popular_science","id":"5585","status":"public"}]},"publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","degree_awarded":"PhD","file":[{"embargo":"2020-05-02","file_id":"6373","checksum":"c0085d47c58c9cbcab1b0a783480f6da","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.pdf","date_created":"2019-05-03T11:54:52Z","creator":"cigler","file_size":12597663,"date_updated":"2021-02-11T11:17:13Z"},{"checksum":"2eac954de1c8bbf7e6fb35ed0221ae8c","file_id":"6374","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed","file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.docx","date_created":"2019-05-03T11:54:54Z","file_size":34644426,"date_updated":"2020-07-14T12:47:28Z","creator":"cigler"}],"language":[{"iso":"eng"}],"alternative_title":["ISTA Thesis"],"month":"05","abstract":[{"text":"Decades of studies have revealed the mechanisms of gene regulation in molecular detail. We make use of such well-described regulatory systems to explore how the molecular mechanisms of protein-protein and protein-DNA interactions shape the dynamics and evolution of gene regulation. \r\n\r\ni) We uncover how the biophysics of protein-DNA binding determines the potential of regulatory networks to evolve and adapt, which can be captured using a simple mathematical model. \r\nii) The evolution of regulatory connections can lead to a significant amount of crosstalk between binding proteins. We explore the effect of crosstalk on gene expression from a target promoter, which seems to be modulated through binding competition at non-specific DNA sites. \r\niii) We investigate how the very same biophysical characteristics as in i) can generate significant fitness costs for cells through global crosstalk, meaning non-specific DNA binding across the genomic background. \r\niv) Binding competition between proteins at a target promoter is a prevailing regulatory feature due to the prevalence of co-regulation at bacterial promoters. However, the dynamics of these systems are not always straightforward to determine even if the molecular mechanisms of regulation are known. A detailed model of the biophysical interactions reveals that interference between the regulatory proteins can constitute a new, generic form of system memory that records the history of the input signals at the promoter. \r\n\r\nWe demonstrate how the biophysics of protein-DNA binding can be harnessed to investigate the principles that shape and ultimately limit cellular gene regulation. These results provide a basis for studies of higher-level functionality, which arises from the underlying regulation. \r\n","lang":"eng"}],"oa_version":"Published Version","author":[{"id":"46613666-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia","full_name":"Igler, Claudia","last_name":"Igler"}],"article_processing_charge":"No","title":"On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation","citation":{"mla":"Igler, Claudia. On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6371.","ieee":"C. Igler, “On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation,” Institute of Science and Technology Austria, 2019.","short":"C. Igler, On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation, Institute of Science and Technology Austria, 2019.","ama":"Igler C. On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. 2019. doi:10.15479/AT:ISTA:6371","apa":"Igler, C. (2019). On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6371","chicago":"Igler, Claudia. “On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6371.","ista":"Igler C. 2019. On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. Institute of Science and Technology Austria."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","project":[{"_id":"251EE76E-B435-11E9-9278-68D0E5697425","grant_number":"24573","name":"Design principles underlying genetic switch architecture (DOC Fellowship)"}],"page":"152","date_published":"2019-05-03T00:00:00Z","doi":"10.15479/AT:ISTA:6371","date_created":"2019-05-03T11:55:51Z","has_accepted_license":"1","year":"2019","day":"03","publisher":"Institute of Science and Technology Austria","oa":1},{"language":[{"iso":"eng"}],"file":[{"file_name":"2018_NatureEcology_Igler.pdf","date_created":"2020-05-14T11:28:52Z","creator":"dernst","file_size":1135973,"date_updated":"2020-07-14T12:47:37Z","checksum":"383a2e2c944a856e2e821ec8e7bf71b6","file_id":"7830","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"publication_status":"published","ec_funded":1,"related_material":{"record":[{"relation":"popular_science","id":"5585","status":"public"},{"relation":"dissertation_contains","status":"public","id":"6371"}]},"issue":"10","volume":2,"oa_version":"Submitted Version","abstract":[{"lang":"eng","text":"Gene regulatory networks evolve through rewiring of individual components—that is, through changes in regulatory connections. However, the mechanistic basis of regulatory rewiring is poorly understood. Using a canonical gene regulatory system, we quantify the properties of transcription factors that determine the evolutionary potential for rewiring of regulatory connections: robustness, tunability and evolvability. In vivo repression measurements of two repressors at mutated operator sites reveal their contrasting evolutionary potential: while robustness and evolvability were positively correlated, both were in trade-off with tunability. Epistatic interactions between adjacent operators alleviated this trade-off. A thermodynamic model explains how the differences in robustness, tunability and evolvability arise from biophysical characteristics of repressor–DNA binding. The model also uncovers that the energy matrix, which describes how mutations affect repressor–DNA binding, encodes crucial information about the evolutionary potential of a repressor. The biophysical determinants of evolutionary potential for regulatory rewiring constitute a mechanistic framework for understanding network evolution."}],"intvolume":" 2","month":"09","scopus_import":"1","ddc":["570"],"date_updated":"2024-03-27T23:30:48Z","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"JoBo"}],"file_date_updated":"2020-07-14T12:47:37Z","_id":"67","status":"public","type":"journal_article","article_type":"original","publication":"Nature Ecology and Evolution","day":"10","year":"2018","has_accepted_license":"1","isi":1,"date_created":"2018-12-11T11:44:27Z","date_published":"2018-09-10T00:00:00Z","doi":"10.1038/s41559-018-0651-y","page":"1633 - 1643","oa":1,"quality_controlled":"1","publisher":"Nature Publishing Group","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"apa":"Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., & Guet, C. C. (2018). Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. Nature Publishing Group. https://doi.org/10.1038/s41559-018-0651-y","ama":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2018;2(10):1633-1643. doi:10.1038/s41559-018-0651-y","ieee":"C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Evolutionary potential of transcription factors for gene regulatory rewiring,” Nature Ecology and Evolution, vol. 2, no. 10. Nature Publishing Group, pp. 1633–1643, 2018.","short":"C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology and Evolution 2 (2018) 1633–1643.","mla":"Igler, Claudia, et al. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Nature Ecology and Evolution, vol. 2, no. 10, Nature Publishing Group, 2018, pp. 1633–43, doi:10.1038/s41559-018-0651-y.","ista":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2(10), 1633–1643.","chicago":"Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Nature Ecology and Evolution. Nature Publishing Group, 2018. https://doi.org/10.1038/s41559-018-0651-y."},"title":"Evolutionary potential of transcription factors for gene regulatory rewiring","article_processing_charge":"No","external_id":{"isi":["000447947600021"]},"publist_id":"7987","author":[{"first_name":"Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87","last_name":"Igler","full_name":"Igler, Claudia"},{"full_name":"Lagator, Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato"},{"orcid":"0000-0002-6699-1455","full_name":"Tkacik, Gasper","last_name":"Tkacik","first_name":"Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","first_name":"Jonathan P","last_name":"Bollback","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P"},{"last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"}],"project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"grant_number":"648440","name":"Selective Barriers to Horizontal Gene Transfer","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_id":"251EE76E-B435-11E9-9278-68D0E5697425","name":"Design principles underlying genetic switch architecture (DOC Fellowship)","grant_number":"24573"}]},{"project":[{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440"},{"name":"Design principles underlying genetic switch architecture (DOC Fellowship)","grant_number":"24573","_id":"251EE76E-B435-11E9-9278-68D0E5697425"}],"status":"public","tmp":{"image":"/images/cc_0.png","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","name":"Creative Commons Public Domain Dedication (CC0 1.0)","short":"CC0 (1.0)"},"type":"research_data","_id":"5585","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"file_date_updated":"2020-07-14T12:47:07Z","title":"Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring","article_processing_charge":"No","author":[{"id":"46613666-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia","full_name":"Igler, Claudia","last_name":"Igler"},{"full_name":"Lagator, Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato"},{"first_name":"Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkacik, Gasper","last_name":"Tkacik"},{"first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","last_name":"Bollback"},{"last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["576"],"date_updated":"2024-03-27T23:30:48Z","citation":{"mla":"Igler, Claudia, et al. Data for the Paper Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:108.","ama":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring. 2018. doi:10.15479/AT:ISTA:108","apa":"Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., & Guet, C. C. (2018). Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:108","ieee":"C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring.” Institute of Science and Technology Austria, 2018.","short":"C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, (2018).","chicago":"Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Data for the Paper Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:108.","ista":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring, Institute of Science and Technology Austria, 10.15479/AT:ISTA:108."},"month":"07","oa":1,"publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Mean repression values and standard error of the mean are given for all operator mutant libraries."}],"license":"https://creativecommons.org/publicdomain/zero/1.0/","ec_funded":1,"date_created":"2018-12-12T12:31:40Z","doi":"10.15479/AT:ISTA:108","date_published":"2018-07-20T00:00:00Z","related_material":{"record":[{"relation":"research_paper","id":"67","status":"public"},{"status":"public","id":"6371","relation":"research_paper"}]},"file":[{"file_id":"5611","checksum":"1435781526c77413802adee0d4583cce","access_level":"open_access","relation":"main_file","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","date_created":"2018-12-12T13:02:45Z","file_name":"IST-2018-108-v1+1_data_figures.xlsx","creator":"system","date_updated":"2020-07-14T12:47:07Z","file_size":16507}],"day":"20","datarep_id":"108","year":"2018","has_accepted_license":"1"},{"ddc":["570","576"],"date_updated":"2021-01-12T06:50:39Z","file_date_updated":"2020-07-14T12:44:53Z","department":[{"_id":"CaGu"},{"_id":"JoBo"}],"_id":"1427","status":"public","pubrep_id":"588","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)"},"file":[{"creator":"system","date_updated":"2020-07-14T12:44:53Z","file_size":648115,"date_created":"2018-12-12T10:09:27Z","file_name":"IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"4751","checksum":"1f456ce1d2aa2f67176a1709f9702ecf"}],"language":[{"iso":"eng"}],"publication_status":"published","issue":"3","volume":33,"ec_funded":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner."}],"month":"03","intvolume":" 33","scopus_import":1,"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. 2016. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 33(3), 761–769.","chicago":"Lagator, Mato, Claudia Igler, Anaisa Moreno, Calin C Guet, and Jonathan P Bollback. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv269.","apa":"Lagator, M., Igler, C., Moreno, A., Guet, C. C., & Bollback, J. P. (2016). Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv269","ama":"Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 2016;33(3):761-769. doi:10.1093/molbev/msv269","ieee":"M. Lagator, C. Igler, A. Moreno, C. C. Guet, and J. P. Bollback, “Epistatic interactions in the arabinose cis-regulatory element,” Molecular Biology and Evolution, vol. 33, no. 3. Oxford University Press, pp. 761–769, 2016.","short":"M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology and Evolution 33 (2016) 761–769.","mla":"Lagator, Mato, et al. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University Press, 2016, pp. 761–69, doi:10.1093/molbev/msv269."},"title":"Epistatic interactions in the arabinose cis-regulatory element","author":[{"full_name":"Lagator, Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato"},{"last_name":"Igler","full_name":"Igler, Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia"},{"first_name":"Anaisa","last_name":"Moreno","full_name":"Moreno, Anaisa"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Bollback","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","first_name":"Jonathan P"}],"publist_id":"5772","project":[{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"day":"01","publication":"Molecular Biology and Evolution","has_accepted_license":"1","year":"2016","date_published":"2016-03-01T00:00:00Z","doi":"10.1093/molbev/msv269","date_created":"2018-12-11T11:51:57Z","page":"761 - 769","quality_controlled":"1","publisher":"Oxford University Press","oa":1}]