---
_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:<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>
  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>.
  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. <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>.
  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'
...