ArticleMolecular biology and evolution2016
Epistatic Interactions in the Arabinose Cis-Regulatory Element.
Article in Molecular biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- The adaptive landscapes of three globaleLife · 2026Article
- Nucleotide-level characterization and improvement of l-arabinose- and l-rhamnose-inducible systems in E. coli using a high-throughput approach.Nucleic acids research · 2025Article
- Ultrasound-responsive engineered bacteria mediated specific controlled expression of catalase and efficient radiotherapy.Materials today. Bio · 2025Article
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- Recent Advances in Spatiotemporal Manipulation of Engineered Bacteria for Precision Cancer Therapy.International journal of nanomedicine · 2025Review
- The highly rugged yet navigable regulatory landscape of the bacterial transcription factor TetR.Nature communications · 2024Article
- Environment-dependent epistasis increases phenotypic diversity in gene regulatory networks.Science advances · 2023Article
- Spatiotemporal control of engineered bacteria to express interferon-γ by focused ultrasound for tumor immunotherapy.Nature communications · 2022Article
- Suppressor Mutants: History and Today's Applications.EcoSal Plus · 2021Review
- Mastering the control of the Rho transcription factor for biotechnological applications.Applied microbiology and biotechnology · 2021Review
- Recent insights into the genotype-phenotype relationship from massively parallel genetic assays.Evolutionary applications · 2019Review
- Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution.Molecular systems biology · 2018Article
- Widespread epistasis regulates glucose homeostasis and gene expression.PLoS genetics · 2017Article
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- Emergence of Resistance Mutations inOpen forum infectious diseases · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner.
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