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A robust ultrasensitive transcriptional switch in noisy cellular environments

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Title
A robust ultrasensitive transcriptional switch in noisy cellular environments
Author(s)
Eui Min Jeong; Jae Kyoung Kim
Publication Date
2024-03
Journal
npj Systems Biology and Applications, v.10, no.1
Publisher
Systems Biology Instititute | Nature Publishing Group
Abstract
Ultrasensitive transcriptional switches enable sharp transitions between transcriptional on and off states and are essential for cells to respond to environmental cues with high fidelity. However, conventional switches, which rely on direct repressor-DNA binding, are extremely noise-sensitive, leading to unintended changes in gene expression. Here, through model simulations and analysis, we discovered that an alternative design combining three indirect transcriptional repression mechanisms, sequestration, blocking, and displacement, can generate a noise-resilient ultrasensitive switch. Although sequestration alone can generate an ultrasensitive switch, it remains sensitive to noise because the unintended transcriptional state induced by noise persists for long periods. However, by jointly utilizing blocking and displacement, these noise-induced transitions can be rapidly restored to the original transcriptional state. Because this transcriptional switch is effective in noisy cellular contexts, it goes beyond previous synthetic transcriptional switches, making it particularly valuable for robust synthetic system design. Our findings also provide insights into the evolution of robust ultrasensitive switches in cells. Specifically, the concurrent use of seemingly redundant indirect repression mechanisms in diverse biological systems appears to be a strategy to achieve noise-resilience of ultrasensitive switches.
URI
https://pr.ibs.re.kr/handle/8788114/15120
DOI
10.1038/s41540-024-00356-2
ISSN
2056-7189
Appears in Collections:
Pioneer Research Center for Mathematical and Computational Sciences(수리 및 계산과학 연구단) > Biomedical Mathematics Group(의생명 수학 그룹) > 1. Journal Papers (저널논문)
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