Urbano Arthur, Smith Jim, Weeks Robert J, Chatterjee Aniruddha
Department of Pathology, Dunedin School of Medicine, University of Otago, 56 Hanover Street, Dunedin 9054, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, 3A Symonds Street, Private Bag 92019, Auckland, New Zealand.
Cancers (Basel). 2019 Oct 9;11(10):1515. doi: 10.3390/cancers11101515.
DNA methylation is the most widely-studied epigenetic modification, playing a critical role in the regulation of gene expression. Dysregulation of DNA methylation is implicated in the pathogenesis of numerous diseases. For example, aberrant DNA methylation in promoter regions of tumor-suppressor genes has been strongly associated with the development and progression of many different tumors. Accordingly, technologies designed to manipulate DNA methylation at specific genomic loci are very important, especially in the context of cancer therapy. Traditionally, epigenomic editing technologies have centered around zinc finger proteins (ZFP)- and transcription activator-like effector protein (TALE)-based targeting. More recently, however, the emergence of clustered regulatory interspaced short palindromic repeats (CRISPR)-deactivated Cas9 (dCas9)-based editing systems have shown to be a more specific and efficient method for the targeted manipulation of DNA methylation. Here, we describe the regulation of the DNA methylome, its significance in cancer and the current state of locus-specific editing technologies for altering DNA methylation.
DNA甲基化是研究最为广泛的表观遗传修饰，在基因表达调控中发挥着关键作用。DNA甲基化失调与多种疾病的发病机制有关。例如，肿瘤抑制基因启动子区域的异常DNA甲基化与许多不同肿瘤的发生和发展密切相关。因此，旨在在特定基因组位点操纵DNA甲基化的技术非常重要，尤其是在癌症治疗的背景下。传统上，表观基因组编辑技术主要围绕基于锌指蛋白（ZFP）和转录激活样效应蛋白（TALE）的靶向作用。然而，最近出现的基于成簇规律间隔短回文重复序列（CRISPR）-失活的Cas9（dCas9）编辑系统已被证明是一种更特异、高效的靶向操纵DNA甲基化的方法。在此，我们描述了DNA甲基化组的调控、其在癌症中的意义以及用于改变DNA甲基化的位点特异性编辑技术的现状。
