{"related_material":{"record":[{"id":"5585","status":"public","relation":"popular_science"},{"status":"public","id":"67","relation":"part_of_dissertation"}]},"_id":"6371","doi":"10.15479/AT:ISTA:6371","title":"On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation","type":"dissertation","language":[{"iso":"eng"}],"publisher":"IST Austria","month":"05","supervisor":[{"last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"}],"publication_status":"published","citation":{"chicago":"Igler, Claudia. <i>On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation</i>. IST Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6371\">https://doi.org/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>. IST Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6371\">https://doi.org/10.15479/AT:ISTA:6371</a>","ieee":"C. Igler, <i>On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation</i>. IST Austria, 2019.","ista":"Igler C. 2019. On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation, IST Austria, 152p.","short":"C. Igler, On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation, IST Austria, 2019.","ama":"Igler C. <i>On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation</i>. IST Austria; 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6371\">10.15479/AT:ISTA:6371</a>","mla":"Igler, Claudia. <i>On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation</i>. IST Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6371\">10.15479/AT:ISTA:6371</a>."},"author":[{"id":"46613666-F248-11E8-B48F-1D18A9856A87","full_name":"Igler, Claudia","last_name":"Igler","first_name":"Claudia"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"keyword":["gene regulation","biophysics","transcription factor binding","bacteria"],"alternative_title":["IST Austria Thesis"],"date_updated":"2020-08-11T10:10:41Z","has_accepted_license":"1","file":[{"file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.pdf","relation":"main_file","file_id":"6373","checksum":"c0085d47c58c9cbcab1b0a783480f6da","date_created":"2019-05-03T11:54:52Z","file_size":12597663,"access_level":"open_access","creator":"cigler","content_type":"application/pdf","date_updated":"2020-07-14T12:47:28Z"},{"creator":"cigler","embargo_to":"open_access","access_level":"closed","file_size":34644426,"date_updated":"2020-07-14T12:47:28Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.docx","relation":"source_file","file_id":"6374","date_created":"2019-05-03T11:54:54Z","checksum":"2eac954de1c8bbf7e6fb35ed0221ae8c"}],"day":"03","project":[{"grant_number":"24573","_id":"251EE76E-B435-11E9-9278-68D0E5697425","name":"Design principles underlying genetic switch architecture (DOC Fellowship)"}],"date_published":"2019-05-03T00:00:00Z","department":[{"_id":"CaGu"}],"ddc":["576","579"],"status":"public","file_date_updated":"2020-07-14T12:47:28Z","publication_identifier":{"issn":["2663-337X"]},"oa_version":"Published Version","year":"2019","date_created":"2019-05-03T11:55:51Z","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"}],"page":"152"}