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The RNA N6-methyladenosine modification landscape of human fetal tissues.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2019-04-29 , DOI: 10.1038/s41556-019-0315-4
Shan Xiao 1 , Shuo Cao 1 , Qitao Huang 2 , Linjian Xia 3 , Mingqiang Deng 1 , Mengtian Yang 1 , Guiru Jia 1 , Xiaona Liu 1 , Junfang Shi 1 , Weishi Wang 1 , Yuan Li 1 , Sun Liu 1 , Haoran Zhu 1 , Kaifen Tan 1 , Qizhi Luo 4 , Mei Zhong 2 , Chunjiang He 3 , Laixin Xia 1
Affiliation  

A single genome gives rise to diverse tissues through complex epigenomic mechanisms, including N6-methyladenosine (m6A), a widespread RNA modification that is implicated in many biological processes. Here, to explore the global landscape of m6A in human tissues, we generated 21 whole-transcriptome m6A methylomes across major fetal tissues using m6A sequencing. These data reveal dynamic m6A methylation, identify large numbers of tissue differential m6A modifications and indicate that m6A is positively correlated with gene expression homeostasis. We also report m6A methylomes of long intergenic non-coding RNA (lincRNA), finding that enhancer lincRNAs are enriched for m6A. Tissue m6A regions are often enriched for single nucleotide polymorphisms that are associated with the expression of quantitative traits and complex traits including common diseases, which may potentially affect m6A modifications. Finally, we find that m6A modifications preferentially occupy genes with CpG-rich promoters, features of which regulate RNA transcript m6A. Our data indicate that m6A is widely regulated by human genetic variation and promoters, suggesting a broad involvement of m6A in human development and disease.

中文翻译:

人类胎儿组织的 RNA N6-甲基腺苷修饰景观。

单个基因组通过复杂的表观基因组机制产生不同的组织,包括 N6-甲基腺苷 (m6A),这是一种广泛的 RNA 修饰,涉及许多生物过程。在这里,为了探索人体组织中 m6A 的全球格局,我们使用 m6A 测序在主要胎儿组织中生成了 21 个全转录组 m6A 甲基化组。这些数据揭示了动态 m6A 甲基化,鉴定了大量组织差异 m6A 修饰,并表明 m6A 与基因表达稳态正相关。我们还报告了长基因间非编码 RNA (lincRNA) 的 m6A 甲基化组,发现增强子 lincRNA 富含 m6A。组织 m6A 区域通常富含与数量性状和复杂性状(包括常见疾病)的表达相关的单核苷酸多态性,这可能会影响 m6A 修饰。最后,我们发现 m6A 修饰优先占据具有富含 CpG 启动子的基因,其特征调节 RNA 转录物 m6A。我们的数据表明 m6A 受到人类遗传变异和启动子的广泛调控,表明 m6A 广泛参与人类发育和疾病。
更新日期:2019-05-16
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