Quantitative LC-MS Provides No Evidence for m6dA or m4dC in the Genome of Mouse Embryonic Stem Cells and Tissues
Quantitative LC-MS Provides No Evidence for m6dA or m4dC in the Genome of Mouse Embryonic Stem Cells and Tissues
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DOI：
10.1002/anie.201700424
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发表时间：
2017-09-04
影响因子：
16.6
通讯作者：
Carell, Thomas
中科院分区：
文献类型：
--
作者：
Schiffers, Sarah;Ebert, Charlotte;Carell, Thomas
直到最近，人们才相信高等生物的基因组除了包含四种典型的DNA碱基外，还仅包含5-甲基-dC（m（5）dC）作为控制表观遗传过程的修饰碱基。近年来，随着干细胞和脑组织DNA中5-羟甲基-dC（hmdC）、5-甲酰基-dC（fdC）和5-羧基-dC（cadC）的发现，这一观点发生了巨大变化。N-6-甲基脱氧腺苷（m（6）dA）是最近报道的存在于各种真核生物基因组中的碱基。该碱基与N-4-甲基脱氧胞苷（m（4）dC）一起首次被报道为细菌基因组的组成部分。在这项工作中，我们研究了这些潜在的表观遗传相关的DNA碱基的水平和分布，通过使用一种新的超灵敏的UHPLC-MS方法。我们进一步报告了m（5）dC、hmdC、fdC和cadC的定量数据，但我们无法在从小鼠胚胎干细胞或脑和肝组织分离的DNA中检测到m（4）dC或m（6）dA，这对其表观遗传相关性提出了质疑。
Until recently, it was believed that the genomes of higher organisms contain, in addition to the four canonical DNA bases, only 5-methyl-dC (m(5)dC) as a modified base to control epigenetic processes. In recent years, this view has changed dramatically with the discovery of 5-hydroxymethyl-dC (hmdC), 5-formyl-dC (fdC), and 5-carboxy-dC (cadC) in DNA from stem cells and brain tissue. N-6-methyldeoxyadenosine (m(6)dA) is the most recent base reported to be present in the genome of various eukaryotic organisms. This base, together with N-4-methyldeoxycytidine (m(4)dC), was first reported to be a component of bacterial genomes. In this work, we investigated the levels and distribution of these potentially epigenetically relevant DNA bases by using a novel ultrasensitive UHPLC-MS method. We further report quantitative data for m(5)dC, hmdC, fdC, and cadC, but we were unable to detect either m(4)dC or m(6)dA in DNA isolated from mouse embryonic stem cells or brain and liver tissue, which calls into question their epigenetic relevance.