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哺乳动物中转座元件的 DNA 甲基化动态。

DNA methylation dynamics at transposable elements in mammals.

机构信息

Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, München D-81377, Germany.

出版信息

Essays Biochem. 2019 Dec 20;63(6):677-689. doi: 10.1042/EBC20190039.

Abstract

Transposable elements dominate the mammalian genome, but their contribution to genetic and epigenetic regulation has been largely overlooked. This was in part due to technical limitations, which made the study of repetitive sequences at single copy resolution difficult. The advancement of next-generation sequencing assays in the last decade has greatly enhanced our understanding of transposable element function. In some instances, specific transposable elements are thought to have been co-opted into regulatory roles during both mouse and human development, while in disease such regulatory potential can contribute to malignancy. DNA methylation is arguably the best characterised regulator of transposable element activity. DNA methylation is associated with transposable element repression, and acts to limit their genotoxic potential. In specific developmental contexts, erasure of DNA methylation is associated with a burst of transposable element expression. Developmental regulation of DNA methylation enables transposon activation, ensuring their survival and propagation throughout the host genome, and also allows the host access to regulatory sequences encoded within the elements. Here I discuss DNA methylation at transposable elements, describing its function and dynamic regulation throughout murine and human development.

摘要

转座元件在哺乳动物基因组中占主导地位,但它们在遗传和表观遗传调控中的作用在很大程度上被忽视了。这在一定程度上是由于技术限制,使得研究单拷贝分辨率的重复序列变得困难。在过去十年中,下一代测序技术的进步极大地提高了我们对转座元件功能的理解。在某些情况下,特定的转座元件被认为在小鼠和人类发育过程中被共同用于调节作用,而在疾病中,这种调节潜力可能导致恶性肿瘤。

DNA 甲基化可以说是转座元件活性的最佳调节因子。DNA 甲基化与转座元件的抑制有关,其作用是限制它们的遗传毒性潜力。在特定的发育环境中,DNA 甲基化的消除与转座元件表达的爆发有关。DNA 甲基化在发育过程中的调控使转座子激活,确保它们在宿主基因组中的存活和传播,并使宿主能够访问元件内编码的调节序列。

在这里,我将讨论转座元件上的 DNA 甲基化,描述其在小鼠和人类发育过程中的功能和动态调控。

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