Increased understanding of the impact of environmental exposures on the epigenome.
Increased understanding of the impact of environmental exposures on the epigenome.
复制标题
增加对环境暴露对表观基因组影响的了解。
DOI：
10.1002/em.21843
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发表时间：
2014
影响因子：
2.8
通讯作者：
Tang,Wan-Yee
中科院分区：
文献类型：
--
作者：
O'Hagan,HeatherM;Tang,Wan-Yee
环境毒物暴露会导致多种疾病的发生。最近的研究表明，接触这些毒物会导致 DNA 甲基化、微小 RNA 表达和组蛋白修饰发生改变 [Hou et al., 2012]。根据定义，这些表观遗传变化是有丝分裂遗传的，并影响基因表达，它们可能在建立与毒物暴露相关的疾病表型中发挥作用，特别是当暴露发生在发育和其他关键生命阶段时[Cortessis et al., 2011]。表观遗传学领域在技术、方法和数据采集方面正在经历快速进步，从而能够识别因急性和长期暴露而发生表观遗传学改变的多个基因组位点。了解暴露后会发生哪些表观遗传变化、何时发生以及如何监测这些变化，最终将有助于开发暴露的生物标志物，并有望逆转暴露引起的表观遗传变化的治疗方法。本期表观遗传学特刊重点关注环境暴露对表观基因组的影响。本期包括有关人类群体和动物模型的评论、评论和原创研究文章，以证明环境暴露对表观基因组的影响，并在某些情况下将这些变化与疾病表型联系起来。表观遗传学的三个主要组成部分是 DNA 甲基化、组蛋白修饰和小非编码 RNA 表达（Baylin 和 Jones 综述[2013]）。当甲基添加到 DNA 内 CpG 二核苷酸对的胞嘧啶时，就会发生 DNA 甲基化，主要与染色质失活和基因表达抑制相关。 DNA 重复区域和基因间区域中的 CpG 二核苷酸往往高度甲基化。相反，在基因的启动子中，有称为 CpG 岛的 CpG 二核苷酸密集区域，这些区域往往是非甲基化的，从而允许相关基因的表达。环境暴露与整体和重复元件 DNA 甲基化水平的降低以及特定 CpG 岛启动子中 DNA 甲基化的增加和减少有关（Cortessis 等人[2011] 和 Hou 等人[2012] 综述）。
Environmental toxicant exposure contributes to the development of a diverse array of diseases. Recent work has demonstrated that exposure to these toxicants causes alterations in DNA methylation, expression of micro-RNAs, and histone modifications [Hou et al., 2012]. As by definition, these epigenetic changes are mitotically heritable and affect gene expression, they likely play a role in establishing disease phenotypes associated with toxicant exposure, particularly when exposures occur during development and other critical life stages [Cortessis et al., 2011]. The field of epigenetics is undergoing a rapid advancement in technology, methodology, and data acquisition allowing for the identification of multiple genomic loci that are epigenetically altered with both acute and prolonged exposure. The understanding of what epigenetic changes occur in response to exposure, when they occur and how to monitor them will ultimately allow for the development of biomarkers of exposure and hopefully treatments that reverse exposure-induced epigenetic changes. This special issue on epigenetics focusses on the impact of environmental exposures on the epigenome. The issue includes reviews, commentaries, and original research articles on both human cohorts and animal models to demonstrate the impact of environmental exposure on the epigenome and, in some cases, link these changes to disease phenotype.The three main components of epigenetics are DNA methylation, histone modification, and small noncoding RNA expression (reviewed in Baylin and Jones [2013]). DNA methylation occurs when a methyl group is added to the cytosine of a CpG dinucleotide pair within the DNA and is mostly associated with inactive chromatin and repressed gene expression. CpG dinucleotides in repetitive and intergenic regions of DNA tend to be highly methylated. In contrast, in the promoters of genes there are dense regions of CpG dinucleotides called CpG islands that tend to be unmethylated allowing for expression of the associated gene. Environmental exposures have been linked to decreases in levels of global and repeat element DNA methylation, as well as gains and losses of DNA methylation in specific CpG islandcontaining promoters (reviewed in Cortessis et al.[2011] and Hou et al.[2012]).