ArticleProceedings of the National Academy of Sciences of the United States of America2010
Bimodal gene expression in noncooperative regulatory systems.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 107 citations in OpenAlex.
- Bimodality in pan-cancer proteomics reveals new opportunities for biomarker discovery.Genome biology · 2026Article
- The Interplay Between Non-Instantaneous Dynamics of mRNA and Bounded Extrinsic Stochastic Perturbations for a Self-Enhancing Transcription Factor.Entropy (Basel, Switzerland) · 2026Article
- Monitoring Molecular Uptake and Cancer Cells' Response by Development of Quantitative Drug Derivative Probes for Chemical Imaging.Analytical chemistry · 2025Article
- Collateral mutagenesis funnels multiple sources of DNA damage into a ubiquitous mutational signature.bioRxiv : the preprint server for biology · 2025Article
- Ocelli: an open-source tool for the analysis and visualization of developmental multimodal single-cell data.NAR genomics and bioinformatics · 2025Article
- Single-cell analyses reveal increased gene expression variability in human neurodevelopmental conditions.American journal of human genetics · 2025Article
- Population-level control of two manganese oxidases expands the niche for bacterial manganese biomineralization.NPJ biofilms and microbiomes · 2025Article
- Bimodality in E. coli gene expression: Sources and robustness to genome-wide stresses.PLoS computational biology · 2025Article
- TGF-β1 promotes osteogenesis of mesenchymal stem cells via integrin mediated mechanical positive autoregulation.iScience · 2024Article
- Synthetic genetic circuits to uncover the OCT4 trajectories of successful reprogramming of human fibroblasts.Science advances · 2023Article
- A Genetically Encoded Biosensor for the Detection of Levulinic Acid.Journal of microbiology and biotechnology · 2023Article
- Boolean modeling of mechanosensitive epithelial to mesenchymal transition and its reversal.iScience · 2023Article
- Conserved Molecular Players Involved in Human Nose Morphogenesis Underlie Evolution of the Exaggerated Snout Phenotype in Cichlids.Genome biology and evolution · 2023Article
- Inferring transcriptional bursting kinetics from single-cell snapshot data using a generalized telegraph model.Royal Society open science · 2023Article
- An integrated approach to identify bimodal genes associated with prognosis in câncer.Genetics and molecular biology · 2021Article
- Fluctuating-rate model with multiple gene states.Journal of mathematical biology · 2020Article
- Multi-modality in gene regulatory networks with slow promoter kinetics.PLoS computational biology · 2019Article
- Linear mapping approximation of gene regulatory networks with stochastic dynamics.Nature communications · 2018Article
- Single-Cell RNA Sequencing: A New Window into Cell Scale Dynamics.Biophysical journal · 2018Review
- Circuit-Host Coupling Induces Multifaceted Behavioral Modulations of a Gene Switch.Biophysical journal · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bimodality of gene expression, as a mechanism contributing to phenotypic diversity, enhances the survival of cells in a fluctuating environment. To date, the bimodal response of a gene regulatory system has been attributed to the cooperativity of transcription factor binding or to feedback loops. It has remained unclear whether noncooperative binding of transcription factors can give rise to bimodality in an open-loop system. We study a theoretical model of gene expression in a two-step cascade (a deterministically monostable system) in which the regulatory gene produces transcription factors that have a nonlinear effect on the activity of the target gene. We show that a unimodal distribution of transcription factors over the cell population can generate a bimodal steady-state output without cooperative transcription factor binding. We introduce a simple method of geometric construction that allows one to predict the onset of bimodality. The construction only involves the parameters of bursting of the regulatory gene and the dose-response curve of the target gene. Using this method, we show that the gene expression may switch between unimodal and bimodal as the concentration of inducers or corepressors is varied. These findings may explain the experimentally observed bimodal response of cascades consisting of a fluorescent protein reporter controlled by the tetracycline repressor. The geometric construction provides a useful tool for designing experiments and for interpretation of their results. Our findings may have important implications for understanding the strategies adopted by cell populations to survive in changing environments.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.