--- _id: '6371' abstract: - lang: eng 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" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Claudia full_name: Igler, Claudia id: 46613666-F248-11E8-B48F-1D18A9856A87 last_name: Igler citation: 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. 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. 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. 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. 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. date_created: 2019-05-03T11:55:51Z date_published: 2019-05-03T00:00:00Z date_updated: 2024-02-21T13:45:52Z day: '03' ddc: - '576' - '579' degree_awarded: PhD department: - _id: CaGu doi: 10.15479/AT:ISTA:6371 file: - access_level: open_access checksum: c0085d47c58c9cbcab1b0a783480f6da content_type: application/pdf creator: cigler date_created: 2019-05-03T11:54:52Z date_updated: 2021-02-11T11:17:13Z embargo: 2020-05-02 file_id: '6373' file_name: IglerClaudia_OntheNatureofGeneRegulatoryDesign.pdf file_size: 12597663 relation: main_file - access_level: closed checksum: 2eac954de1c8bbf7e6fb35ed0221ae8c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cigler date_created: 2019-05-03T11:54:54Z date_updated: 2020-07-14T12:47:28Z embargo_to: open_access file_id: '6374' file_name: IglerClaudia_OntheNatureofGeneRegulatoryDesign.docx file_size: 34644426 relation: source_file file_date_updated: 2021-02-11T11:17:13Z has_accepted_license: '1' keyword: - gene regulation - biophysics - transcription factor binding - bacteria language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '152' project: - _id: 251EE76E-B435-11E9-9278-68D0E5697425 grant_number: '24573' name: Design principles underlying genetic switch architecture (DOC Fellowship) publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '67' relation: part_of_dissertation status: public - id: '5585' relation: popular_science status: public status: public supervisor: - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 title: On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ...