The dynamic epigenome and its implications in toxicology

被引:138
作者
Szyf, Moshe [1 ]
机构
[1] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada
基金
加拿大健康研究院;
关键词
DNA methylation; DNA demethylation; anti cancer agents; epigenetics; chromatin structure; chromatin modification; histone acetylation; histone methylation; histone acetyltransferase; histone deacetylase; histone methyltransferase; DNA methyltransferase; DNA demethylase; global hypo-methylation; HDAC inhibitors;
D O I
10.1093/toxsci/kfm177
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The epigenome serves as an interface between the dynamic environment and the inherited static genome. The epigenome is comprised of chromatin and a covalent modification of DNA by methylation. The epigenome is sculpted during development to shape the diversity of gene expression programs in the different cell types of the organism by a highly organized process. Epigenetic aberrations have similar consequences to genetic polymorphisms resulting in variations in gene function. Recent data suggest that the epigenome is dynamic and is therefore responsive to environmental signals not only during the critical periods in development but also later in life as well. It is postulated here that not only chemicals but also exposure to social behavior, such as maternal care, could affect the epigenome. It is proposed that exposures to different environmental agents could lead to interindividual phenotypic diversity as well as differential susceptibility to disease and behavioral pathologies. Interindividual differences in the epigenetic state could also affect susceptibility to xenobiotics. Although our current understanding of how epigenetic mechanisms impact on the toxic action of xenobiotics is very limited, it is anticipated that in the future, epigenetics will be incorporated in the assessment of the safety of chemicals.
引用
收藏
页码:7 / 23
页数:17
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