ArticleNucleic acids research2014
What makes the lac-pathway switch: identifying the fluctuations that trigger phenotype switching in gene regulatory systems.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- The impact of metabolism on the adaptation of organisms to environmental change.Frontiers in cell and developmental biology · 2023Article
- Using average transcription level to understand the regulation of stochastic gene activation.Royal Society open science · 2022Article
- Switching off: The phenotypic transition to the uninduced state of the lactose uptake pathway.Biophysical journal · 2022Article
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- Synthetic gene-regulatory networks in the opportunistic human pathogenProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Signaling pathways have an inherent need for noise to acquire information.BMC bioinformatics · 2020Article
- Relatively slow stochastic gene-state switching in the presence of positive feedback significantly broadens the region of bimodality through stabilizing the uninduced phenotypic state.PLoS computational biology · 2018Article
- Monitoring single-cell gene regulation under dynamically controllable conditions with integrated microfluidics and software.Nature communications · 2018Article
- Bistability and Nonmonotonic Induction of the lac Operon in the Natural Lactose Uptake System.Biophysical journal · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multistable gene regulatory systems sustain different levels of gene expression under identical external conditions. Such multistability is used to encode phenotypic states in processes including nutrient uptake and persistence in bacteria, fate selection in viral infection, cell-cycle control and development. Stochastic switching between different phenotypes can occur as the result of random fluctuations in molecular copy numbers of mRNA and proteins arising in transcription, translation, transport and binding. However, which component of a pathway triggers such a transition is generally not known. By linking single-cell experiments on the lactose-uptake pathway in E. coli to molecular simulations, we devise a general method to pinpoint the particular fluctuation driving phenotype switching and apply this method to the transition between the uninduced and induced states of the lac-genes. We find that the transition to the induced state is not caused only by the single event of lac-repressor unbinding, but depends crucially on the time period over which the repressor remains unbound from the lac-operon. We confirm this notion in strains with a high expression level of the lac-repressor (leading to shorter periods over which the lac-operon remains unbound), which show a reduced switching rate. Our techniques apply to multistable gene regulatory systems in general and allow to identify the molecular mechanisms behind stochastic transitions in gene regulatory circuits.
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