---
_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'
...
---
_id: '5556'
abstract:
- lang: eng
  text: "MATLAB code and processed datasets available for reproducing the results
    in: \r\nLukačišin, M.*, Landon, M.*, Jajoo, R*. (2016) Sequence-Specific Thermodynamic
    Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking
    in Yeast.\r\n*equal contributions"
article_processing_charge: No
author:
- first_name: Martin
  full_name: Lukacisin, Martin
  id: 298FFE8C-F248-11E8-B48F-1D18A9856A87
  last_name: Lukacisin
  orcid: 0000-0001-6549-4177
- first_name: Matthieu
  full_name: Landon, Matthieu
  last_name: Landon
- first_name: Rishi
  full_name: Jajoo, Rishi
  last_name: Jajoo
citation:
  ama: Lukacisin M, Landon M, Jajoo R. MATLAB analysis code for “Sequence-Specific
    Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing
    and Backtracking in Yeast.” 2016. doi:<a href="https://doi.org/10.15479/AT:ISTA:45">10.15479/AT:ISTA:45</a>
  apa: Lukacisin, M., Landon, M., &#38; Jajoo, R. (2016). MATLAB analysis code for
    “Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional
    Pausing and Backtracking in Yeast.” Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/AT:ISTA:45">https://doi.org/10.15479/AT:ISTA:45</a>
  chicago: Lukacisin, Martin, Matthieu Landon, and Rishi Jajoo. “MATLAB Analysis Code
    for ‘Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both
    Transcriptional Pausing and Backtracking in Yeast.’” Institute of Science and
    Technology Austria, 2016. <a href="https://doi.org/10.15479/AT:ISTA:45">https://doi.org/10.15479/AT:ISTA:45</a>.
  ieee: M. Lukacisin, M. Landon, and R. Jajoo, “MATLAB analysis code for ‘Sequence-Specific
    Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing
    and Backtracking in Yeast.’” Institute of Science and Technology Austria, 2016.
  ista: Lukacisin M, Landon M, Jajoo R. 2016. MATLAB analysis code for ‘Sequence-Specific
    Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing
    and Backtracking in Yeast’, Institute of Science and Technology Austria, <a href="https://doi.org/10.15479/AT:ISTA:45">10.15479/AT:ISTA:45</a>.
  mla: Lukacisin, Martin, et al. <i>MATLAB Analysis Code for “Sequence-Specific Thermodynamic
    Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking
    in Yeast.”</i> Institute of Science and Technology Austria, 2016, doi:<a href="https://doi.org/10.15479/AT:ISTA:45">10.15479/AT:ISTA:45</a>.
  short: M. Lukacisin, M. Landon, R. Jajoo, (2016).
datarep_id: '45'
date_created: 2018-12-12T12:31:31Z
date_published: 2016-08-25T00:00:00Z
date_updated: 2024-02-21T13:51:53Z
day: '25'
ddc:
- '571'
department:
- _id: ToBo
doi: 10.15479/AT:ISTA:45
file:
- access_level: open_access
  checksum: ee697f2b1ade4dc14d6ac0334dd832ab
  content_type: application/zip
  creator: system
  date_created: 2018-12-12T13:02:58Z
  date_updated: 2020-07-14T12:47:02Z
  file_id: '5616'
  file_name: IST-2016-45-v1+1_PaperCode.zip
  file_size: 296722548
  relation: main_file
file_date_updated: 2020-07-14T12:47:02Z
has_accepted_license: '1'
keyword:
- transcription
- pausing
- backtracking
- polymerase
- RNA
- NET-seq
- nucleosome
- basepairing
license: https://creativecommons.org/licenses/by-sa/4.0/
month: '08'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '8431'
    relation: used_in_publication
    status: deleted
  - id: '1029'
    relation: research_paper
    status: public
status: public
title: MATLAB analysis code for 'Sequence-Specific Thermodynamic Properties of Nucleic
  Acids Influence Both Transcriptional Pausing and Backtracking in Yeast'
tmp:
  image: /images/cc_by_sa.png
  legal_code_url: https://creativecommons.org/licenses/by-sa/4.0/legalcode
  name: Creative Commons Attribution-ShareAlike 4.0 International Public License (CC
    BY-SA 4.0)
  short: CC BY-SA (4.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2016'
...
---
_id: '6161'
abstract:
- lang: eng
  text: 'The tra-1 gene is a terminal regulator of somatic sex in Caenorhabditis elegans:
    high tra-1 activity elicits female development, low tra-1 activity elicits male
    development. To investigate the function and evolution of tra- 1, we examined
    the tra-1 gene from the closely related nematode C. briggsae. Ce-tra-1 and Cb-tra-1
    are unusually divergent. Each gene generates two transcripts, but only one of
    these is present in both species. This common transcript encodes TRA-1A, which
    shows only 44% amino acid identity between the species, a figure much lower than
    that for previously compared genes. A Cb-tra-1 transgene rescues many tissues
    of tra-1(null) mutants of C. elegans but not the somatic gonad or germ line. This
    transgene also causes nongonadal feminization of XO animals, indicating incorrect
    sexual regulation. Alignment of Ce-TRA-1A and Cb-TRA-1A defined several conserved
    regions likely to be important for tra-1 function. The phenotype differences between
    Ce-tra- 1(null) mutants rescued by Cb-tra-1 transgenes and wild-type C. elegans
    indicate significant divergence of regulatory regions. These molecular and functional
    studies suggest that evolution of sex determination in nematodes is rapid and
    genetically complex.'
author:
- first_name: Mario
  full_name: de Bono, Mario
  id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87
  last_name: de Bono
  orcid: 0000-0001-8347-0443
- first_name: J.
  full_name: Hodgkin, J.
  last_name: Hodgkin
citation:
  ama: 'de Bono M, Hodgkin J. Evolution of sex determination in Caenorhabditis: Unusually
    high divergence of tra-1 and its functional consequences. <i>Genetics</i>. 1996;144(2):587-595.'
  apa: 'de Bono, M., &#38; Hodgkin, J. (1996). Evolution of sex determination in Caenorhabditis:
    Unusually high divergence of tra-1 and its functional consequences. <i>Genetics</i>.
    Genetics Society of America.'
  chicago: 'Bono, Mario de, and J. Hodgkin. “Evolution of Sex Determination in Caenorhabditis:
    Unusually High Divergence of Tra-1 and Its Functional Consequences.” <i>Genetics</i>.
    Genetics Society of America, 1996.'
  ieee: 'M. de Bono and J. Hodgkin, “Evolution of sex determination in Caenorhabditis:
    Unusually high divergence of tra-1 and its functional consequences,” <i>Genetics</i>,
    vol. 144, no. 2. Genetics Society of America, pp. 587–595, 1996.'
  ista: 'de Bono M, Hodgkin J. 1996. Evolution of sex determination in Caenorhabditis:
    Unusually high divergence of tra-1 and its functional consequences. Genetics.
    144(2), 587–595.'
  mla: 'de Bono, Mario, and J. Hodgkin. “Evolution of Sex Determination in Caenorhabditis:
    Unusually High Divergence of Tra-1 and Its Functional Consequences.” <i>Genetics</i>,
    vol. 144, no. 2, Genetics Society of America, 1996, pp. 587–95.'
  short: M. de Bono, J. Hodgkin, Genetics 144 (1996) 587–595.
date_created: 2019-03-21T11:50:37Z
date_published: 1996-10-01T00:00:00Z
date_updated: 2021-01-12T08:06:28Z
day: '01'
extern: '1'
external_id:
  pmid:
  - '8889522'
intvolume: '       144'
issue: '2'
keyword:
- amino acid sequence
- article
- caenorhabditis elegans
- evolution
- genetic variability
- nonhuman
- priority journal
- sex determination
- Amino Acid Sequence
- Animals
- Animals
- Genetically Modified
- Base Sequence
- Caenorhabditis
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- DNA
- Helminth
- DNA-Binding Proteins
- Evolution
- Molecular
- Female
- Helminth Proteins
- Membrane Proteins
- Molecular Sequence Data
- Mutagenesis
- RNA
- Messenger
- Sequence Homology
- Amino Acid
- Sex Determination (Analysis)
- Transcription Factors
- Transgenes
- Turner Syndrome
- Animalia
- Caenorhabditis
- Caenorhabditis briggsae
- Caenorhabditis elegans
- Nematoda
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1207552/
month: '10'
oa: 1
oa_version: Published Version
page: 587-595
pmid: 1
publication: Genetics
publication_identifier:
  issn:
  - '00166731'
publication_status: published
publisher: Genetics Society of America
quality_controlled: '1'
status: public
title: 'Evolution of sex determination in Caenorhabditis: Unusually high divergence
  of tra-1 and its functional consequences'
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 144
year: '1996'
...