---
_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'
...