Martos Suzanne N, Tang Wan-Yee, Wang Zhibin
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Prog Biophys Mol Biol. 2015 Jul;118(1-2):44-54. doi: 10.1016/j.pbiomolbio.2015.02.011. Epub 2015 Mar 16.
Epigenetic mechanisms involving DNA methylation, histone modification, histone variants and nucleosome positioning, and noncoding RNAs regulate cell-, tissue-, and developmental stage-specific gene expression by influencing chromatin structure and modulating interactions between proteins and DNA. Epigenetic marks are mitotically inherited in somatic cells and may be altered in response to internal and external stimuli. The idea that environment-induced epigenetic changes in mammals could be inherited through the germline, independent of genetic mechanisms, has stimulated much debate. Many experimental models have been designed to interrogate the possibility of transgenerational epigenetic inheritance and provide insight into how environmental exposures influence phenotypes over multiple generations in the absence of any apparent genetic mutation. Unexpected molecular evidence has forced us to reevaluate not only our understanding of the plasticity and heritability of epigenetic factors, but of the stability of the genome as well. Recent reviews have described the difference between transgenerational and intergenerational effects; the two major epigenetic reprogramming events in the mammalian lifecycle; these two events making transgenerational epigenetic inheritance of environment-induced perturbations rare, if at all possible, in mammals; and mechanisms of transgenerational epigenetic inheritance in non-mammalian eukaryotic organisms. This paper briefly introduces these topics and mainly focuses on (1) transgenerational phenotypes and epigenetic effects in mammals, (2) environment-induced intergenerational epigenetic effects, and (3) the inherent difficulties in establishing a role for epigenetic inheritance in human environmental disease.
涉及DNA甲基化、组蛋白修饰、组蛋白变体和核小体定位以及非编码RNA的表观遗传机制，通过影响染色质结构和调节蛋白质与DNA之间的相互作用，来调控细胞、组织和发育阶段特异性的基因表达。表观遗传标记在体细胞中可进行有丝分裂遗传，并可能因内部和外部刺激而发生改变。环境诱导的哺乳动物表观遗传变化可能通过种系独立于遗传机制进行遗传，这一观点引发了诸多争论。许多实验模型已被设计用于探究跨代表观遗传遗传的可能性，并深入了解在没有任何明显基因突变的情况下，环境暴露如何在多代中影响表型。意外的分子证据迫使我们不仅要重新评估我们对表观遗传因素可塑性和遗传性的理解，还要重新评估基因组的稳定性。最近的综述描述了跨代效应和代际效应之间的差异；哺乳动物生命周期中的两个主要表观遗传重编程事件；这两个事件使得环境诱导的扰动在哺乳动物中进行跨代表观遗传遗传变得极为罕见（如果有可能的话）；以及非哺乳动物真核生物中的跨代表观遗传遗传机制。本文简要介绍了这些主题，并主要关注：（1）哺乳动物中的跨代表型和表观遗传效应；（2）环境诱导的代际表观遗传效应；（3）在确定表观遗传遗传在人类环境疾病中的作用方面存在的固有困难。
