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A Stochastic Single-Molecule Event Triggers Phenotype Switching of a Bacterial Cell
Open accessAbstract
By monitoring fluorescently labeled lactose permease with single-molecule sensitivity, we investigated the molecular mechanism of how an Escherichia coli cell with the lac operon switches from one phenotype to another. At intermediate inducer concentrations, a population of genetically identical cells exhibits two phenotypes: induced cells with highly fluorescent membranes and uninduced cells with a small number of membrane-bound permeases. We found that this basal-level expression results from partial dissociation of the tetrameric lactose repressor from one of its operators on looped DNA. In contrast, infrequent events of complete dissociation of the repressor from DNA result in large bursts of permease expression that trigger induction of the lac operon. Hence, a stochastic single-molecule event determines a cell's phenotype.
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Metadata
- Authors
- Choi, P. J., Cai, L., Frieda, K., & Xie, X. S.
- Affiliations
- Harvard University (US)
- Corresponding author
- Choi, Paul J.
- Cai, Long
- Frieda, Kirsten
- Xie, X. Sunney
- Venue
- Science
- Published
- 2008-10-17
- Volume
- 322
- Issue
- 5900
- Pages
- 442-446
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2819113
- OpenAlex
- W1978182054
- Cited by
- 438
- References
- 28
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 13 · 2023: 11 · 2022: 11 · 2021: 14 · 2020: 21 · 2019: 33 · 2018: 28 · 2017: 26 · 2016: 30 · 2015: 27 · 2014: 35 · 2013: 34 · 2012: 37
- FWCI
- 19.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (DP1OD000277)
- National Institute of Biomedical Imaging and Bioengineering (R01EB010244)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Keywords
- lac operon, lactose permease, lactose repressor, phenotypic switching, stochastic gene expression, single-molecule fluorescence, Escherichia coli, basal expression, gene expression regulation
- MeSH terms
- Bacterial Proteins, Escherichia coli, Lac Operon, Lactose, Microscopy, Fluorescence, Models, Genetic, Monosaccharide Transport Proteins, Operator Regions, Genetic, Phenotype, Recombinant Fusion Proteins, Repressor Proteins, RNA, Messenger, Stochastic Processes, Gene Expression Regulation, Bacterial, Feedback, Physiological, Symporters, Escherichia coli Proteins, Lac Repressors
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