The dynamic epigenome and its implications in toxicology.
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.
Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montréal, Québec H3G 1Y6, Canada. moshe.szyf@mcgill.ca
Moshe
M
Szyf
D000107:Acetylation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D014644:Genetic Variation; D018392:Genomic Imprinting / Q000187:drug effects; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008425:Maternal Behavior / Q000187:drug effects; D009369:Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018570:Risk Assessment; D043922:Toxicogenetics / Q000379:methods; D015262:Xenobiotics / Q000633:toxicity*
D002843:Chromatin; D006657:Histones; D015262:Xenobiotics; D015254:DNA Modification Methylases; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases