期刊
ILAR JOURNAL
卷 53, 期 3-4, 页码 289-305出版社
OXFORD UNIV PRESS
DOI: 10.1093/ilar.53.3-4.289
关键词
developmental basis of disease; environmental epigenetics; epigenetic memories; exposome; histone modification; low-dose effects; susceptible windows; ten-eleven translocations; 5 '-hydroxylmethylcytosine
资金
- National Institutes of Health [R01CA112532, P30ES006096, P50ES015905, U01ES019480, U01ES020988, R01ES015584, RC2ES018758, RC2ES018789]
- Veterans Affairs [I01BX000675]
- NATIONAL CANCER INSTITUTE [R01CA112532] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P50ES015905, RC2ES018789, R01ES015584, U01ES019480, U01ES020988, RC2ES018758, P30ES006096] Funding Source: NIH RePORTER
This review focuses on how environmental factors through epigenetics modify disease risk and health outcomes. Major epigenetic events, such as histone modifi cations, DNA methylation, and microRNA expression, are described. The function of dose, duration, composition, and window of exposure in remodeling the individual's epigenetic terrain and disease susceptibility are addressed. The ideas of lifelong editing of early-life epigenetic memories, transgenerational effects through germline transmission, and the potential role of hydroxylmethylation of cytosine in developmental reprogramming are discussed. Finally, the epigenetic effects of several major classes of environmental factors are reviewed in the context of pathogenesis of disease. These include endocrine disruptors, tobacco smoke, polycyclic aromatic hydrocarbons, infectious pathogens, particulate matter, diesel exhaust particles, dust mites, fungi, heavy metals, and other indoor and outdoor pollutants. We conclude that the summation of epigenetic modifi cations induced by multiple environmental exposures, accumulated over time, represented as broad or narrow, acute or chronic, developmental or lifelong, may provide a more precise assessment of risk and consequences. Future investigations may focus on their use as readouts or biomarkers of the totality of past exposure for the prediction of future disease risk and the prescription of effective countermeasures.
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