Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Science. 2018 Sep 28;361(6409):1336-1340. doi: 10.1126/science.aat6806.
The classical model of cytosine DNA methylation (the presence of 5-methylcytosine, 5mC) regulation depicts this covalent modification as a stable repressive regulator of promoter activity. However, whole-genome analysis of 5mC reveals widespread tissue- and cell type-specific patterns and pervasive dynamics during mammalian development. Here we review recent findings that delineate 5mC functions in developmental stages and diverse genomic compartments as well as discuss the molecular mechanisms that connect transcriptional regulation and 5mC. Beyond the newly appreciated dynamics, regulatory roles for 5mC have been suggested in new biological contexts, such as learning and memory or aging. The use of new single-cell measurement techniques and precise editing tools will enable functional analyses of 5mC in gene expression, clarifying its role in various biological processes.
经典的胞嘧啶 DNA 甲基化(5-甲基胞嘧啶,5mC 的存在)调控模型将这种共价修饰描绘为启动子活性的稳定抑制调节剂。然而,对 5mC 的全基因组分析揭示了在哺乳动物发育过程中广泛存在的组织和细胞类型特异性模式和普遍的动态变化。在这里,我们回顾了最近的发现,这些发现描绘了 5mC 在发育阶段和不同基因组区室中的功能,以及讨论了连接转录调控和 5mC 的分子机制。除了新发现的动态变化外,5mC 在新的生物学背景下的调控作用也被提出,例如学习和记忆或衰老。新的单细胞测量技术和精确的编辑工具的使用将能够对 5mC 在基因表达中的功能进行分析,从而阐明其在各种生物学过程中的作用。