Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1289/EHP1937 |
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 | |
Chappell, Grace A.1,2; Israel, Jennifer W.3; Simon, Jeremy M.3; Pott, Sebastian4; Safi, Alexias5; Eklund, Karl3; Sexton, Kenneth G.2; Bodnar, Wanda2; Lieb, Jason D.4; Crawford, Gregory E.5; Rusyn, Ivan1; Furey, Terrence S.3,6,7 | |
2017-10-01 | |
发表期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES
![]() |
ISSN | 0091-6765 |
EISSN | 1552-9924 |
出版年 | 2017 |
卷号 | 125期号:10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | 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 viva 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. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000413793300018 |
WOS关键词 | CHIP-SEQ ; EXPRESSION ; EXPOSURE ; CANCER ; RATS ; SP1 ; EXONUCLEASE-1 ; GENOTOXICITY ; MECHANISMS ; CADMIUM |
WOS类目 | Environmental Sciences ; Public, Environmental & Occupational Health ; Toxicology |
WOS研究方向 | Environmental Sciences & Ecology ; Public, Environmental & Occupational Health ; Toxicology |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/23168 |
专题 | 资源环境科学 |
作者单位 | 1.Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77843 USA; 2.Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27514 USA; 3.Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA; 4.Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA; 5.Duke Univ, Dept Pediat, Duke Ctr Genom & Computat Biol, Durham, NC 27710 USA; 6.Univ N Carolina, Dept Biol, Chapel Hill, NC 27514 USA; 7.Univ N Carolina, Sch Med, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA |
推荐引用方式 GB/T 7714 | Chappell, Grace A.,Israel, Jennifer W.,Simon, Jeremy M.,et al. 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[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2017,125(10). |
APA | Chappell, Grace A..,Israel, Jennifer W..,Simon, Jeremy M..,Pott, Sebastian.,Safi, Alexias.,...&Furey, Terrence S..(2017).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.ENVIRONMENTAL HEALTH PERSPECTIVES,125(10). |
MLA | Chappell, Grace A.,et al."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".ENVIRONMENTAL HEALTH PERSPECTIVES 125.10(2017). |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论