{"ddc":["576","579"],"status":"public","title":"On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation","keyword":["gene regulation","biophysics","transcription factor binding","bacteria"],"file_date_updated":"2021-02-11T11:17:13Z","date_published":"2019-05-03T00:00:00Z","date_created":"2019-05-03T11:55:51Z","oa_version":"Published Version","article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","has_accepted_license":"1","publication_identifier":{"issn":["2663-337X"]},"type":"dissertation","month":"05","project":[{"name":"Design principles underlying genetic switch architecture (DOC Fellowship)","grant_number":"24573","_id":"251EE76E-B435-11E9-9278-68D0E5697425"}],"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"}],"related_material":{"record":[{"id":"67","status":"public","relation":"part_of_dissertation"},{"relation":"popular_science","status":"public","id":"5585"}]},"department":[{"_id":"CaGu"}],"alternative_title":["ISTA Thesis"],"citation":{"mla":"Igler, Claudia. <i>On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6371\">10.15479/AT:ISTA:6371</a>.","apa":"Igler, C. (2019). <i>On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6371\">https://doi.org/10.15479/AT:ISTA:6371</a>","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.","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. <a href=\"https://doi.org/10.15479/AT:ISTA:6371\">https://doi.org/10.15479/AT:ISTA:6371</a>.","ama":"Igler C. On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6371\">10.15479/AT:ISTA:6371</a>","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.","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."},"degree_awarded":"PhD","author":[{"id":"46613666-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia","last_name":"Igler","full_name":"Igler, Claudia"}],"publication_status":"published","language":[{"iso":"eng"}],"oa":1,"day":"03","year":"2019","publisher":"Institute of Science and Technology Austria","_id":"6371","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","page":"152","file":[{"file_id":"6373","relation":"main_file","date_updated":"2021-02-11T11:17:13Z","checksum":"c0085d47c58c9cbcab1b0a783480f6da","creator":"cigler","file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.pdf","access_level":"open_access","date_created":"2019-05-03T11:54:52Z","content_type":"application/pdf","file_size":12597663,"embargo":"2020-05-02"},{"embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":34644426,"date_created":"2019-05-03T11:54:54Z","file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.docx","access_level":"closed","creator":"cigler","checksum":"2eac954de1c8bbf7e6fb35ed0221ae8c","date_updated":"2020-07-14T12:47:28Z","relation":"source_file","file_id":"6374"}],"doi":"10.15479/AT:ISTA:6371"}