ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Baseline Chromatin Modification Levels May Predict Interindividual Variability in Ozone-Induced Gene Expression.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Toxicological Effects of Air Pollutants on Human Airway Cell Models Using Air-liquid Interface Systems: A Systematic Review.Current environmental health reports · 2025Pooled it
- Review
- Quantitative estimates of inter-individual variability for new approach methodologies-based systemic safety toolbox using a population-based human in vitro model.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Transcriptomic-based roadmap to the healthy and ozone-exposed lung.Current opinion in toxicology · 2024Article
- New approach methodologies (NAMs) for theFrontiers in toxicology · 2024Review
- Are active efflux transporters contributing to infant drug exposure via breastmilk? A longitudinal study.Basic & clinical pharmacology & toxicology · 2022Article
- Ozone Responsive Gene Expression as a Model for Describing Repeat Exposure Response Trajectories and Interindividual Toxicodynamic Variability In Vitro.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Macrophage activation in the lung during the progression of nitrogen mustard induced injury is associated with histone modifications and altered miRNA expression.Toxicology and applied pharmacology · 2021Article
- Role of Innate Immune System in Environmental Lung Diseases.Current allergy and asthma reports · 2021Review
- Linking inter-individual variability to endocrine disruptors: insights for epigenetic inheritance.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Article
- Application of epigenetic data in human health risk assessment.Current opinion in toxicology · 2017Article
- Air Pollution and the Epigenome: A Model Relationship for the Exploration of Toxicoepigenetics.Current opinion in toxicology · 2017Article
- In vitro exposure systems and dosimetry assessment tools for inhaled tobacco products: Workshop proceedings, conclusions and paths forward for in vitro model use.Alternatives to laboratory animals : ATLA · 2017Article
- Using Chromatin Immunoprecipitation in Toxicology: A Step-by-Step Guide to Increasing Efficiency, Reducing Variability, and Expanding Applications.Current protocols in toxicology · 2017Article
- Linking the Epigenome with Exposure Effects and Susceptibility: The Epigenetic Seed and Soil Model.Toxicological sciences : an official journal of the Society of Toxicology · 2017Review
- The Next Generation of Risk Assessment Multi-Year Study-Highlights of Findings, Applications to Risk Assessment, and Future Directions.Environmental health perspectives · 2016Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Traditional toxicological paradigms have relied on factors such as age, genotype, and disease status to explain variability in responsiveness to toxicant exposure; however, these are neither sufficient to faithfully identify differentially responsive individuals nor are they modifiable factors that can be leveraged to mitigate the exposure effects. Unlike these factors, the epigenome is dynamic and shaped by an individual's environment. We sought to determine whether baseline levels of specific chromatin modifications correlated with the interindividual variability in their ozone (O3)-mediated induction in an air-liquid interface model using primary human bronchial epithelial cells from a panel of 11 donors. We characterized the relationship between the baseline abundance of 6 epigenetic markers with established roles as key regulators of gene expression-histone H3 lysine 4 trimethylation (H3K4me3), H3K27 acetylation (H3K27ac), pan-acetyl H4 (H4ac), histone H3K27 di/trimethylation (H3K27me2/3), unmodified H3, and 5-hydroxymethylcytosine (5-hmC)-and the variability in the O3-induced expression of IL-8, IL-6, COX2, and HMOX1. Baseline levels of H3K4me3, H3K27me2/3, and 5-hmC, but not H3K27ac, H4ac, and total H3, correlated with the interindividual variability in O3-mediated induction of HMOX1 and COX2. In contrast, none of the chromatin modifications that we examined correlated with the induction of IL-8 and IL-6. From these findings, we propose an "epigenetic seed and soil" model in which chromatin modification states between individuals differ in the relative abundance of specific modifications (the "soil") that govern how receptive the gene is to toxicant-mediated cellular signals (the "seed") and thus regulate the magnitude of exposure-related gene induction.
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Registered trials
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.