Landscape and Regulation of m6A and m6Am Methylome across Human and Mouse Tissues

Landscape and Regulation of m6A and m6Am Methylome across Human and Mouse Tissues
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人类和小鼠组织中 m6A 和 m6Am 甲基化组的景观和调节。

DOI:
10.1016/j.molcel.2019.09.032
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发表时间:
2020-01-16
期刊:
影响因子:
16
通讯作者:
Yi, Chengqi
Yi, Chengqi
中科院分区:
生物学1区
文献类型:
--
作者:
Liu, Jun'e;Li, Kai;Yi, Chengqi

文献摘要

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N-6-甲基腺苷(m(6)A),最丰富的内部mRNA修饰,和N-6,2 '-O-二甲基腺苷(m(6)Am),发现于第一个转录的核苷酸,是两种可逆的表位转录组学标记。然而,m(6)A和m(6)Am在人和小鼠组织中的分布和分布模式的特征很差。在这里,我们通过分析43个人类和16个小鼠组织报告了m(6)A和m(6)Am甲基化组,并证明了脑组织的最强组织特异性。组织特异性m(6)A峰的小子集也可以容易地对组织类型进行分类。总体m(6)A和m(6)Am水平与其书写者和擦除者的表达水平部分相关。此外,含有m(6)A的区域富含SNP。此外,跨物种分析表明,物种,而不是组织类型是甲基化的主要决定因素。总的来说,我们的研究提供了一个深入的资源,解剖景观和调节的m(6)A和m(6)Am epitranscriptomic标记在哺乳动物组织。
N-6-methyladenosine (m(6)A), the most abundant internal mRNA modification, and N-6,2'-O-dimethyladenosine (m(6)Am), found at the first-transcribed nucleotide, are two reversible epitranscriptomic marks. However, the profiles and distribution patterns of m(6)A and m(6)Am across human and mouse tissues are poorly characterized. Here, we report the m(6)A and m(6)Am methylome through profiling of 43 human and 16 mouse tissues and demonstrate strongest tissue specificity for the brain tissues. A small subset of tissue-specific m(6)A peaks can also readily classify tissue types. The overall m(6)A and m(6)Am level is partially correlated with the expression level of their writers and erasers. Additionally, the m(6)A-containing regions are enriched for SNPs. Furthermore, cross-species analysis revealed that species rather than tissue type is the primary determinant of methylation. Collectively, our study provides an in-depth resource for dissecting the landscape and regulation of the m(6)A and m(6)Am epitranscriptomic marks across mammalian tissues.