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DNA甲基化的动力学及上下文依赖作用

Dynamics and Context-Dependent Roles of DNA Methylation.

作者信息

Ambrosi Christina, Manzo Massimiliano, Baubec Tuncay

机构信息

Department of Molecular Mechanisms of Disease, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland; Molecular Life Sciences PhD Program of the Life Sciences Zurich Graduate School, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.

Department of Molecular Mechanisms of Disease, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.

出版信息

J Mol Biol. 2017 May 19;429(10):1459-1475. doi: 10.1016/j.jmb.2017.02.008. Epub 2017 Feb 16.

Abstract

DNA methylation is one of the most extensively studied epigenetic marks. It is involved in transcriptional gene silencing and plays important roles during mammalian development. Its perturbation is often associated with human diseases. In mammalian genomes, DNA methylation is a prevalent modification that decorates the majority of cytosines. It is found at the promoters and enhancers of inactive genes, at repetitive elements, and within transcribed gene bodies. Its presence at promoters is dynamically linked to gene activity, suggesting that it could directly influence gene expression patterns and cellular identity. The genome-wide distribution and dynamic behaviour of this mark have been studied in great detail in a variety of tissues and cell lines, including early embryonic development and in embryonic stem cells. In combination with functional studies, these genome-wide maps of DNA methylation revealed interesting features of this mark and provided important insights into its dynamic nature and potential functional role in genome regulation. In this review, we discuss how these recent observations, in combination with insights obtained from biochemical and functional genetics studies, have expanded our current knowledge about the regulation and context-dependent roles of DNA methylation in mammalian genomes.

摘要

DNA甲基化是研究最为广泛的表观遗传标记之一。它参与转录基因沉默,在哺乳动物发育过程中发挥重要作用。其紊乱常与人类疾病相关。在哺乳动物基因组中,DNA甲基化是一种普遍存在的修饰,修饰了大多数胞嘧啶。它存在于沉默基因的启动子和增强子、重复元件以及转录基因体内。它在启动子处的存在与基因活性动态相关,表明它可能直接影响基因表达模式和细胞特性。在包括早期胚胎发育和胚胎干细胞在内的多种组织和细胞系中,对这种标记的全基因组分布和动态行为进行了详细研究。结合功能研究,这些DNA甲基化的全基因组图谱揭示了这种标记的有趣特征,并为其动态性质及其在基因组调控中的潜在功能作用提供了重要见解。在本综述中,我们讨论了这些最新观察结果,结合从生化和功能遗传学研究中获得的见解,如何扩展了我们目前对哺乳动物基因组中DNA甲基化调控及其依赖于上下文的作用的认识。

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