---
OA_place: publisher
_id: '6071'
abstract:
- lang: eng
  text: 'Transcription factors, by binding to specific sequences on the DNA, control
    the precise spatio-temporal expression of genes inside a cell. However, this specificity
    is limited, leading to frequent incorrect binding of transcription factors that
    might have deleterious consequences on the cell. By constructing a biophysical
    model of TF-DNA binding in the context of gene regulation, I will first explore
    how regulatory constraints can strongly shape the distribution of a population
    in sequence space. Then, by directly linking this to a picture of multiple types
    of transcription factors performing their functions simultaneously inside the
    cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions
    between transcription factors and binding sites that lead to erroneous regulatory
    states -- and understand the constraints this places on the design of regulatory
    systems. I will then develop a generic theoretical framework to investigate the
    coevolution of multiple transcription factors and multiple binding sites, in the
    context of a gene regulatory network that performs a certain function. As a particular
    tractable version of this problem, I will consider the evolution of two transcription
    factors when they transmit upstream signals to downstream target genes. Specifically,
    I will describe the evolutionary steady states and the evolutionary pathways involved,
    along with their timescales, of a system that initially undergoes a transcription
    factor duplication event. To connect this important theoretical model to the prominent
    biological event of transcription factor duplication giving rise to paralogous
    families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription
    factors, a major family in humans, and focus on the patterns of evolution that
    paralogs have undergone in their various protein domains in the recent past. '
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Roshan
  full_name: Prizak, Roshan
  id: 4456104E-F248-11E8-B48F-1D18A9856A87
  last_name: Prizak
citation:
  ama: Prizak R. Coevolution of transcription factors and their binding sites in sequence
    space. 2019. doi:<a href="https://doi.org/10.15479/at:ista:th6071">10.15479/at:ista:th6071</a>
  apa: Prizak, R. (2019). <i>Coevolution of transcription factors and their binding
    sites in sequence space</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:th6071">https://doi.org/10.15479/at:ista:th6071</a>
  chicago: Prizak, Roshan. “Coevolution of Transcription Factors and Their Binding
    Sites in Sequence Space.” Institute of Science and Technology Austria, 2019. <a
    href="https://doi.org/10.15479/at:ista:th6071">https://doi.org/10.15479/at:ista:th6071</a>.
  ieee: R. Prizak, “Coevolution of transcription factors and their binding sites in
    sequence space,” Institute of Science and Technology Austria, 2019.
  ista: Prizak R. 2019. Coevolution of transcription factors and their binding sites
    in sequence space. Institute of Science and Technology Austria.
  mla: Prizak, Roshan. <i>Coevolution of Transcription Factors and Their Binding Sites
    in Sequence Space</i>. Institute of Science and Technology Austria, 2019, doi:<a
    href="https://doi.org/10.15479/at:ista:th6071">10.15479/at:ista:th6071</a>.
  short: R. Prizak, Coevolution of Transcription Factors and Their Binding Sites in
    Sequence Space, Institute of Science and Technology Austria, 2019.
corr_author: '1'
date_created: 2019-03-06T16:16:10Z
date_published: 2019-03-11T00:00:00Z
date_updated: 2026-04-08T13:54:25Z
day: '11'
ddc:
- '576'
degree_awarded: PhD
department:
- _id: GaTk
- _id: NiBa
doi: 10.15479/at:ista:th6071
file:
- access_level: open_access
  checksum: e60a72de35d270b31f1a23d50f224ec0
  content_type: application/pdf
  creator: rprizak
  date_created: 2019-03-06T16:05:07Z
  date_updated: 2020-07-14T12:47:18Z
  file_id: '6072'
  file_name: Thesis_final_PDFA_RoshanPrizak.pdf
  file_size: 20995465
  relation: main_file
- access_level: closed
  checksum: 67c2630333d05ebafef5f018863a8465
  content_type: application/zip
  creator: rprizak
  date_created: 2019-03-06T16:09:39Z
  date_updated: 2020-07-14T12:47:18Z
  file_id: '6073'
  file_name: thesis_v2_merge.zip
  file_size: 85705272
  relation: source_file
  title: Latex files
file_date_updated: 2020-07-14T12:47:18Z
fulldoi: https://doi.org/10.15479/at:ista:th6071
has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: '189'
project:
- _id: 254E9036-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P28844-B27
  name: Biophysics of information processing in gene regulation
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '955'
    relation: part_of_dissertation
    status: public
  - id: '1358'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
title: Coevolution of transcription factors and their binding sites in sequence space
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2019'
...