About: Variation in DNA-Damage Responses to an Inhalational Carcinogen (1,3-Butadiene) in Relation to Strain-Specific Differences in Chromatin Accessibility and Gene Transcription Profiles in C57BL/6J and CAST/EiJ Mice

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About: Variation in DNA-Damage Responses to an Inhalational Carcinogen (1,3-Butadiene) in Relation to Strain-Specific Differences in Chromatin Accessibility and Gene Transcription Profiles in C57BL/6J and CAST/EiJ Mice Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Variation in DNA-Damage Responses to an Inhalational Carcinogen (1,3-Butadiene) in Relation to Strain-Specific Differences in Chromatin Accessibility and Gene Transcription Profiles in C57BL/6J and CAST/EiJ Mice
Creator	Bodnar, Wanda Eklund, Karl Pott, Sebastian Rusyn, Ivan Safi, Alexias Chappell, Grace Crawford, Gregory Furey, Terrence Israel, Jennifer Lieb, Jason Sexton, Kenneth Simon, Jeremy
Source	Medline; PMC
abstract	BACKGROUND: The damaging effects of exposure to environmental toxicants differentially affect genetically distinct individuals, but the mechanisms contributing to these differences are poorly understood. Genetic variation affects the establishment of the gene regulatory landscape and thus gene expression, and we hypothesized that this contributes to the observed heterogeneity in individual responses to exogenous cellular insults. OBJECTIVES: We performed an in vivo study of how genetic variation and chromatin organization may dictate susceptibility to DNA damage, and influence the cellular response to such damage, caused by an environmental toxicant. MATERIALS AND METHODS: We measured DNA damage, messenger RNA (mRNA) and microRNA (miRNA) expression, and genome-wide chromatin accessibility in lung tissue from two genetically divergent inbred mouse strains, C57BL/6J and CAST/EiJ, both in unexposed mice and in mice exposed to a model DNA-damaging chemical, 1,3-butadiene. RESULTS: Our results showed that unexposed CAST/EiJ and C57BL/6J mice have very different chromatin organization and transcription profiles in the lung. Importantly, in unexposed CAST/EiJ mice, which acquired relatively less 1,3-butadiene-induced DNA damage, we observed increased transcription and a more accessible chromatin landscape around genes involved in detoxification pathways. Upon chemical exposure, chromatin was significantly remodeled in the lung of C57BL/6J mice, a strain that acquired higher levels of 1,3-butadiene–induced DNA damage, around the same genes, ultimately resembling the molecular profile of CAST/EiJ. CONCLUSIONS: These results suggest that strain-specific changes in chromatin and transcription in response to chemical exposure lead to a “compensation” for underlying genetic-driven interindividual differences in the baseline chromatin and transcriptional state. This work represents an example of how chemical and environmental exposures can be evaluated to better understand gene-by-environment interactions, and it demonstrates the important role of chromatin response in transcriptomic changes and, potentially, in deleterious effects of exposure. https://doi.org/10.1289/EHP1937
has issue date	2017-10-16(xsd:dateTime)
bibo:doi	10.1289/ehp1937
bibo:pmid	29038090
has license	no-cc
sha1sum (hex)	ee13a8332bcf2df6a68e2190a337a0cbaa161281
schema:url	https://doi.org/10.1289/ehp1937
resource representing a document's title	Variation in DNA-Damage Responses to an Inhalational Carcinogen (1,3-Butadiene) in Relation to Strain-Specific Differences in Chromatin Accessibility and Gene Transcription Profiles in C57BL/6J and CAST/EiJ Mice
has PubMed Central identifier	PMC5944832
has PubMed identifier	29038090
schema:publication	Environ Health Perspect
resource representing a document's body	covid:ee13a8332bcf2df6a68e2190a337a0cbaa161281#body_text
is schema:about of	covid:arg/ee13a8332bcf2df6a68e2190a337a0cbaa161281 named entity 'mRNA' named entity 'p-value' named entity 'up-regulated' named entity 'C57BL/6J' named entity 'C57BL/6J' named entity 'C57BL/6J' named entity 'interleukin 17' named entity 'C57BL/6J' named entity '1,3-butadiene' named entity 'chromatin accessibility' named entity 'transcriptional' named entity 'mice' named entity 'chromatin' named entity 'lung' named entity '1,3-butadiene' named entity 'miRNA' named entity 'inbred mouse strains' named entity 'chromatin organization' named entity 'chemical exposure' named entity 'mice' named entity 'DNA damage' named entity 'mice' named entity 'chromatin organization' named entity 'mice' named entity 'Carcinogen' named entity 'Chromatin Accessibility' named entity 'histone modifications' named entity 'standard deviation' named entity 'downregulation' named entity 'DNA damage' named entity 'C57BL/6J' named entity 'C57BL/6J' named entity 'target sites' named entity 'chromatin' named entity 'metabolic' named entity 'C57BL/6J' named entity 'Monte Carlo simulation' named entity 'phase I metabolism' named entity 'genetically diverse' named entity 'epoxide' named entity 'glutathione' named entity '1,3-butadiene' named entity 'detoxification' named entity 'gene expression' named entity 'repressor' named entity 'chromatin accessibility' named entity 'reactome' named entity 'gene expression' named entity 'gene expression' named entity 'Mafk' named entity 'metabolic' named entity 'miRNAs' named entity 'chromatin landscape' named entity 'conjugation' named entity 'genomic regulatory' named entity 'transposase' named entity '1,3-butadiene' named entity 'gene regulatory' named entity 'generalized linear model' named entity 'pharmaceutical drugs' named entity 'C57BL/6J' named entity 'RNA' named entity 'Mus musculus domesticus' named entity 'carcinogens' named entity '1,3-butadiene' named entity '1,3-butadiene' named entity 'respiratory infection' named entity 'liver' named entity 'NIH'

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