Transcription factor competition facilitates self-sustained oscillations in single gene genetic circuits.
Journal
PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
20
02
2023
accepted:
18
09
2023
revised:
11
10
2023
medline:
12
10
2023
pubmed:
29
9
2023
entrez:
29
9
2023
Statut:
epublish
Résumé
Genetic feedback loops can be used by cells to regulate internal processes or to keep track of time. It is often thought that, for a genetic circuit to display self-sustained oscillations, a degree of cooperativity is needed in the binding and unbinding of actor species. This cooperativity is usually modeled using a Hill function, regardless of the actual promoter architecture. Furthermore, genetic circuits do not operate in isolation and often transcription factors are shared between different promoters. In this work we show how mathematical modelling of genetic feedback loops can be facilitated with a mechanistic fold-change function that takes into account the titration effect caused by competing binding sites for transcription factors. The model shows how the titration effect facilitates self-sustained oscillations in a minimal genetic feedback loop: a gene that produces its own repressor directly without cooperative transcription factor binding. The use of delay-differential equations leads to a stability contour that predicts whether a genetic feedback loop will show self-sustained oscillations, even when taking the bursty nature of transcription into account.
Identifiants
pubmed: 37773967
doi: 10.1371/journal.pcbi.1011525
pii: PCOMPBIOL-D-23-00261
pmc: PMC10566692
doi:
Substances chimiques
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1011525Informations de copyright
Copyright: © 2023 Landman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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