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环境表观遗传学。

Environmental epigenetics.

机构信息

Department of Environmental and Occupational Health, Center of Molecular and Genetic Epidemiology, Università degli Studi di Milano and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy.

出版信息

Heredity (Edinb). 2010 Jul;105(1):105-12. doi: 10.1038/hdy.2010.2. Epub 2010 Feb 24.

Abstract

Epigenetics investigates heritable changes in gene expression that occur without changes in DNA sequence. Several epigenetic mechanisms, including DNA methylation and histone modifications, can change genome function under exogenous influence. We review current evidence indicating that epigenetic alterations mediate effects caused by exposure to environmental toxicants. Results obtained from animal models indicate that in utero or early-life environmental exposures produce effects that can be inherited transgenerationally and are accompanied by epigenetic alterations. The search for human equivalents of the epigenetic mechanisms identified in animal models is under way. Recent investigations have identified a number of environmental toxicants that cause altered methylation of human repetitive elements or genes. Some exposures can alter epigenetic states and the same and/or similar epigenetic alterations can be found in patients with the disease of concern. On the basis of current evidence, we propose possible models for the interplay between environmental exposures and the human epigenome. Several investigations have examined the relationship between exposure to environmental chemicals and epigenetics, and have identified toxicants that modify epigenetic states. Whether environmental exposures have transgenerational epigenetic effects in humans remains to be elucidated. In spite of the current limitations, available evidence supports the concept that epigenetics holds substantial potential for furthering our understanding of the molecular mechanisms of environmental toxicants, as well as for predicting health-related risks due to conditions of environmental exposure and individual susceptibility.

摘要

表观遗传学研究基因表达的可遗传变化,而这些变化不涉及 DNA 序列的改变。几种表观遗传机制,包括 DNA 甲基化和组蛋白修饰,可以在外源影响下改变基因组功能。我们综述了目前的证据,表明表观遗传改变介导了环境毒物暴露引起的效应。动物模型的研究结果表明,宫内或生命早期的环境暴露会产生可跨代遗传的效应,并伴有表观遗传改变。正在寻找动物模型中确定的表观遗传机制的人类等效物。最近的研究已经确定了一些环境毒物,这些毒物会导致人类重复元件或基因的甲基化改变。一些暴露可以改变表观遗传状态,并且在关注疾病的患者中可以发现相同和/或相似的表观遗传改变。基于目前的证据,我们提出了环境暴露与人类表观基因组相互作用的可能模型。有几项研究调查了环境化学物质暴露与表观遗传学之间的关系,并确定了一些可以改变表观遗传状态的毒物。环境暴露是否对人类具有跨代的表观遗传效应仍有待阐明。尽管目前存在局限性,但现有证据支持这样一种观点,即表观遗传学为进一步了解环境毒物的分子机制以及预测由于环境暴露和个体易感性条件而导致的健康相关风险提供了很大的潜力。

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