Zebrafish as a model to study the role of DNA methylation in environmental toxicology
Zebrafish as a model to study the role of DNA methylation in environmental toxicology
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DOI：
10.1007/s11356-014-3466-7
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发表时间：
2015-11-01
影响因子：
5.8
通讯作者：
Legler, Juliette
中科院分区：
文献类型：
--
作者：
Kamstra, Jorke H.;Alestrom, Peter;Legler, Juliette
环境表观遗传学是一个快速发展的领域，它研究环境因素如营养、压力和暴露于化合物对表观遗传基因调控的影响。最近的研究表明，脊椎动物暴露于有毒物质与DNA甲基化的变化有关，DNA甲基化是影响基因转录的主要表观遗传机制。斑马鱼是毒理学和发育生物学的一个著名模型，尽管它们与啮齿动物和人类进化距离很远，但它们正在成为环境表观遗传学的一个模型物种。本文综述了斑马鱼发育过程中DNA甲基化的最新研究进展，并与哺乳动物模型进行了比较，以评价斑马鱼作为研究DNA甲基化在环境毒理学中作用的模型。在早期发育过程中，DNA甲基化重编程存在差异，而在后期发育阶段，5-甲基胞嘧啶和5-羟甲基胞嘧啶的组织分布似乎在物种之间以及基本的DNA（去）甲基化机制之间更加保守。迄今为止在哺乳动物中鉴定的所有DNA甲基转移酶都存在于斑马鱼中，以及许多主要的去甲基化途径。然而，斑马鱼似乎缺乏哺乳动物中存在的一些甲基化途径，例如亲本印记。几项研究报告了斑马鱼暴露于环境污染物（如砷、苯并[a]芘和磷酸三（1，3-二氯-2-丙基）酯）后对DNA甲基化的影响。虽然需要更多的研究来检查污染物暴露对DNA甲基化的遗传影响，但最近的数据表明斑马鱼作为环境表观遗传学模型的有用性。
Environmental epigenetics is a rapidly growing field which studies the effects of environmental factors such as nutrition, stress, and exposure to compounds on epigenetic gene regulation. Recent studies have shown that exposure to toxicants in vertebrates is associated with changes in DNA methylation, a major epigenetic mechanism affecting gene transcription. Zebra fish, a well-known model in toxicology and developmental biology, are emerging as a model species in environmental epigenetics despite their evolutionary distance to rodents and humans. In this review, recent insights in DNA methylation during zebra fish development are discussed and compared to mammalian models in order to evaluate zebra fish as a model to study the role of DNA methylation in environmental toxicology. Differences exist in DNA methylation reprogramming during early development, whereas in later developmental stages, tissue distribution of both 5-methylcytosine and 5-hydroxymethylcytosine seems more conserved between species, as well as basic DNA (de)methylation mechanisms. All DNA methyl transferases identified so far in mammals are present in zebra fish, as well as a number of major demethylation pathways. However, zebra fish appear to lack some methylation pathways present in mammals, such as parental imprinting. Several studies report effects on DNA methylation in zebra fish following exposure to environmental contaminants, such as arsenic, benzo[a]pyrene, and tris(1,3-dichloro-2-propyl)phosphate. Though more research is needed to examine heritable effects of contaminant exposure on DNA methylation, recent data suggests the usefulness of the zebra fish as a model in environmental epigenetics.