The RNA N6-methyladenosine modification landscape of human fetal tissues
The RNA N6-methyladenosine modification landscape of human fetal tissues
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人类胎儿组织的 RNA N-6-甲基腺苷修饰景观
DOI：
10.1038/s41556-019-0315-4
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发表时间：
2019-05-01
影响因子：
21.3
通讯作者：
Xia, Laixin
中科院分区：
文献类型：
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作者：
Xiao, Shan;Cao, Shuo;Xia, Laixin
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N-6-甲基腺苷（m（6）A），这是一种广泛存在的RNA修饰，涉及许多生物过程。在这里，为了探索人类组织中m（6）A的全球景观，我们使用m（6）A测序在主要胎儿组织中产生了21个全转录组m（6）A甲基化组。这些数据揭示了动态的m（6）A甲基化，鉴定了大量的组织差异m（6）A修饰，并表明m（6）A与基因表达稳态正相关。我们还报道了长基因间非编码RNA（lincRNA）的m（6）A甲基化组，发现增强子lincRNA富含m（6）A。组织m（6）A区域通常富含与数量性状和复杂性状（包括常见疾病）表达相关的单核苷酸多态性，这可能潜在地影响m（6）A修饰。最后，我们发现m（6）A修饰优先占据具有富含CpG的启动子的基因，这些启动子的特征调节RNA转录物m（6）A。我们的数据表明，m（6）A广泛受人类遗传变异和启动子的调控，表明m（6）A广泛参与人类发育和疾病。
A single genome gives rise to diverse tissues through complex epigenomic mechanisms, including N-6-methyladenosine (m(6)A), a widespread RNA modification that is implicated in many biological processes. Here, to explore the global landscape of m(6)A in human tissues, we generated 21 whole-transcriptome m(6)A methylomes across major fetal tissues using m(6)A sequencing. These data reveal dynamic m(6)A methylation, identify large numbers of tissue differential m(6)A modifications and indicate that m(6)A is positively correlated with gene expression homeostasis. We also report m(6)A methylomes of long intergenic non-coding RNA (lincRNA), finding that enhancer lincRNAs are enriched for m(6)A. Tissue m(6)A 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 m(6)A modifications. Finally, we find that m(6)A modifications preferentially occupy genes with CpG-rich promoters, features of which regulate RNA transcript m(6)A. Our data indicate that m(6)A is widely regulated by human genetic variation and promoters, suggesting a broad involvement of m(6)A in human development and disease.