State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Sci China Life Sci. 2016 Mar;59(3):219-26. doi: 10.1007/s11427-016-5013-x. Epub 2016 Jan 29.
Epigenetic changes caused by DNA methylation and histone modifications play important roles in the regulation of various cellular processes and development. Recent discoveries of 5-methylcytosine (5mC) oxidation derivatives including 5-hydroxymethylcytosine (5hmC), 5-formylcytsine (5fC) and 5-carboxycytosine (5caC) in mammalian genome further expand our understanding of the epigenetic regulation. Analysis of DNA modification patterns relies increasingly on sequencing-based profiling methods. A number of different approaches have been established to map the DNA epigenomes with single-base resolution, as represented by the bisulfite-based methods, such as classical bisulfite sequencing (BS-seq), TAB-seq (TET-assisted bisulfite sequencing), oxBS-seq (oxidative bisulfite sequencing) and etc. These methods have been used to generate base-resolution maps of 5mC and its oxidation derivatives in genomic samples. The focus of this review will be to discuss the chemical methodologies that have been developed to detect the cytosine derivatives in the genomic DNA.
DNA 甲基化和组蛋白修饰引起的表观遗传变化在调节各种细胞过程和发育中发挥着重要作用。最近在哺乳动物基因组中发现了 5-甲基胞嘧啶（5mC）氧化衍生物，包括 5-羟甲基胞嘧啶（5hmC）、5-甲酰胞嘧啶（5fC）和 5-羧基胞嘧啶（5caC），进一步扩展了我们对表观遗传调控的理解。DNA 修饰模式的分析越来越依赖于基于测序的分析方法。已经建立了许多不同的方法来以单碱基分辨率绘制 DNA 表观基因组图谱，其中包括基于亚硫酸氢盐的方法，如经典亚硫酸氢盐测序（BS-seq）、TAB-seq（TET 辅助亚硫酸氢盐测序）、oxBS-seq（氧化亚硫酸氢盐测序）等。这些方法已被用于生成基因组样本中 5mC 及其氧化衍生物的碱基分辨率图谱。本文综述的重点将是讨论为检测基因组 DNA 中的胞嘧啶衍生物而开发的化学方法学。
