Perera Bambarendage P U, Svoboda Laurie, Dolinoy Dana C
University of Michigan School of Public Health, Department of Environmental Health Sciences, Ann Arbor, MI.
University of Michigan School of Public Health, Department of Nutritional Sciences, Ann Arbor, MI.
Curr Opin Toxicol. 2019 Dec;18:27-33. doi: 10.1016/j.cotox.2019.02.008. Epub 2019 Mar 8.
Epigenetics refers to the study of mitotically heritable and potentially reversible changes in gene expression unrelated to the DNA sequence itself, influenced by epigenetic marks including chromatin modifications, non-coding RNA and alterations to DNA itself via methylation and hydroxymethylation. Epigenetics has taken center stage in the study of diseases such as cancer, diabetes, and neurodegeneration; however, its integration into the field of environmental health sciences and toxicology (e.g. Toxicoepigenetics) is in its infancy. This review highlights the need to evaluate surrogate and target tissues in the field of toxicoepigenetics as the National Institute of Environmental Health Sciences (NIEHS) multi-phased Toxicant Exposure and Response by Genomic and Epigenomic Regulators of Transcription (TaRGET) consortia make headway, and the emergence of non-coding RNA biomarkers. The review also discusses lead (Pb) as a potential toxicoepigenetic exposure, where pre- and post-natal Pb exposure is associated with reprogramming of DNA methylation, histone modifications, and microRNA expression, representing potential biomarkers or predictors for Pb-induced health outcomes. Finally, new advances in epigenome editing, highlighting the potential of small ncRNA, will be explored for environmental health sciences research.
表观遗传学是指对与DNA序列本身无关的基因表达中可遗传且可能可逆的有丝分裂变化的研究,这些变化受表观遗传标记影响,包括染色质修饰、非编码RNA以及通过甲基化和羟甲基化对DNA本身的改变。表观遗传学在癌症、糖尿病和神经退行性疾病等疾病的研究中占据了核心地位;然而,其在环境健康科学和毒理学领域(如毒理表观遗传学)的整合尚处于起步阶段。随着美国国立环境卫生科学研究所(NIEHS)的多阶段“转录组和表观基因组调控因子介导的毒物暴露与反应”(TaRGET)联盟取得进展以及非编码RNA生物标志物的出现,本综述强调了在毒理表观遗传学领域评估替代组织和靶组织的必要性。该综述还讨论了铅(Pb)作为一种潜在的毒理表观遗传暴露因素,产前和产后铅暴露与DNA甲基化、组蛋白修饰和微小RNA表达的重编程有关,这些变化代表了铅诱导健康结果的潜在生物标志物或预测指标。最后,将探讨表观基因组编辑的新进展,突出小非编码RNA在环境健康科学研究中的潜力。