Tost Jörg
CEA - Institut de Génomique, Evry, France.
Methods Mol Biol. 2009;507:3-20. doi: 10.1007/978-1-59745-522-0_1.
DNA methylation occurring on the 5 position of the pyrimidine ring of cytosines in the context of the dinucleotide sequence CpG 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 genomic chromatin landscape. DNA methylation is essential for proper mammalian development, crucial for imprinting, and plays a role in maintaining genomic stability as well as in dosage compensation. 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 in utero development. Aberrant DNA methylation changes have been detected in several diseases, particularly cancer where genome-wide hypomethylation coincides with gene-specific hypermethylation. DNA methylation patterns can be used to detect cancer at very early stages, to classify tumors as well as predict and monitor the response to antineoplastic treatment. As a stable nucleic acid-based modification with limited dynamic range that is technically easy to handle, DNA methylation is a promising biomarker for many applications.
在二核苷酸序列CpG背景下，发生在胞嘧啶嘧啶环5位的DNA甲基化构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，形成基因组染色质景观。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以及剂量补偿中发挥作用。DNA甲基化模式容易因饮食或毒素等环境刺激而发生变化，因此表观基因组在子宫内早期发育阶段似乎最为脆弱。在几种疾病中已检测到异常的DNA甲基化变化，特别是在癌症中，全基因组低甲基化与基因特异性高甲基化同时存在。DNA甲基化模式可用于在非常早期阶段检测癌症、对肿瘤进行分类以及预测和监测对抗肿瘤治疗的反应。作为一种具有有限动态范围且技术上易于处理的基于稳定核酸的修饰，DNA甲基化是许多应用中很有前景的生物标志物。
