Transcription factor competition facilitates self-sustained oscillations in single gene genetic circuits

Jasper Landman*, Sjoerd M. Verduyn Lunel, Willem K. Kegel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article numbere1011525
Number of pages25
JournalPLoS Computational Biology
Volume19
Issue number9
DOIs
Publication statusPublished - Sept 2023

Bibliographical note

Publisher 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.

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