Andersen Gitte Brinch, Tost Jörg
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Laboratory for Epigenetics & Environment, Centre National de Recherche en Génomique Humaine, CEA-Institut de Biologie Francois Jacob, Bâtiment G2, 2 rue Gaston Crémieux, 91000, Evry, France.
Methods Mol Biol. 2018;1708:3-30. doi: 10.1007/978-1-4939-7481-8_1.
DNA methylation at cytosines followed by guanines, CpGs, forms one of the multiple layers of epigenetic mechanisms controlling and modulating gene expression through chromatin structure. It closely interacts with histone modifications and chromatin remodeling complexes to form the local genomic and higher-order chromatin landscape. DNA methylation is essential for proper mammalian development, crucial for imprinting and plays a role in maintaining genomic stability. DNA methylation patterns are susceptible to change in response to environmental stimuli such as diet or toxins, whereby the epigenome seems to be most vulnerable during early life. Changes of DNA methylation levels and patterns have been widely studied in several diseases, especially cancer, where interest has focused on biomarkers for early detection of cancer development, accurate diagnosis, and response to treatment, but have also been shown to occur in many other complex diseases. Recent advances in epigenome engineering technologies allow now for the large-scale assessment of the functional relevance of DNA methylation. As a stable nucleic acid-based modification that is technically easy to handle and which can be analyzed with great reproducibility and accuracy by different laboratories, DNA methylation is a promising biomarker for many applications.
胞嘧啶后接鸟嘌呤（CpG）处的DNA甲基化形成了通过染色质结构控制和调节基因表达的多层表观遗传机制之一。它与组蛋白修饰和染色质重塑复合物密切相互作用，以形成局部基因组和高阶染色质格局。DNA甲基化对于哺乳动物的正常发育至关重要，对印记起关键作用，并在维持基因组稳定性中发挥作用。DNA甲基化模式容易因饮食或毒素等环境刺激而发生变化，由此表观基因组在生命早期似乎最为脆弱。DNA甲基化水平和模式的变化已在多种疾病中得到广泛研究，尤其是癌症，在癌症研究中，人们关注的重点是用于癌症发展早期检测、准确诊断和治疗反应的生物标志物，但也已证明其在许多其他复杂疾病中也会发生。表观基因组工程技术的最新进展现在使得大规模评估DNA甲基化的功能相关性成为可能。作为一种基于核酸的稳定修饰，在技术上易于操作，并且不同实验室能够以高度的可重复性和准确性进行分析，DNA甲基化在许多应用中都是一种很有前景的生物标志物。
