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人类健康与疾病中的环境表观基因组学

Environmental epigenomics in human health and disease.

作者信息

Dolinoy Dana C, Jirtle Randy L

机构信息

Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.

出版信息

Environ Mol Mutagen. 2008 Jan;49(1):4-8. doi: 10.1002/em.20366.

Abstract

The epigenome consists of the DNA methylation marks and histone modifications involved in controlling gene expression. It is accurately reproduced during mitosis and can be inherited transgenerationally. The innate plasticity of the epigenome also enables it to be reprogrammed by nutritional, chemical, and physical factors. Imprinted genes and metastable epialleles represent two classes of genes that are particularly susceptible to environmental factors because their regulation is tightly linked to epigenetic mechanisms. To fully understand the etiology of the most devastating diseases that plague humans, the full complexity of the human epigenome will ultimately need to be characterized. Moreover, the elucidation of the interaction of the environment with the epigenome should allow for the development of novel epigenetic-based diagnostic, prevention, and therapeutic strategies for human diseases. Herein, we introduce the emerging field of environmental epigenomics, discuss the importance of imprinted genes and metastable epialleles as epigenetically labile genomic targets, and endorse the genome-wide identification of the full suite of epigenetically labile targets in both the mouse and human genomes.

摘要

表观基因组由参与控制基因表达的DNA甲基化标记和组蛋白修饰组成。它在有丝分裂过程中能被精确复制,并且可以跨代遗传。表观基因组固有的可塑性也使其能够被营养、化学和物理因素重新编程。印记基因和亚稳定表观等位基因代表了两类特别易受环境因素影响的基因,因为它们的调控与表观遗传机制紧密相连。为了全面了解困扰人类的最具毁灭性疾病的病因,最终需要对人类表观基因组的全部复杂性进行表征。此外,阐明环境与表观基因组的相互作用应该能够开发出基于表观遗传学的新型人类疾病诊断、预防和治疗策略。在此,我们介绍环境表观基因组学这一新兴领域,讨论印记基因和亚稳定表观等位基因作为表观遗传不稳定基因组靶点的重要性,并支持在小鼠和人类基因组中对全套表观遗传不稳定靶点进行全基因组鉴定。

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