Characteristics and homogeneity of N6-methylation in human genomes.
Characteristics and homogeneity of N6-methylation in human genomes.
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人类基因组中 N6-甲基化的特征和同质性。
DOI：
10.1038/s41598-019-41601-7
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发表时间：
2019
影响因子：
4.6
通讯作者：
Pacini CE
中科院分区：
文献类型：
--
作者：
Pacini CE
最近在真核生物基因组中发现了一种新的DNA修饰——N-6甲基化脱氧腺苷（m6dA）。尽管m6dA在真核生物中的丰度很低，但它与癌症等人类疾病有关。因此，准确识别和表征人类基因组中的m6dA是很重要的。在这里，我们在核苷酸水平鉴定m6dA位点，在不同的人类细胞，基因组范围内。我们比较了不同人类细胞之间的m6dA特征，并鉴定了人类基因组中的m6dA特征。我们的数据首次表明，尽管m6dA丰度较低，但m6dA标记确实经常在给定的人类细胞类型的同一基因组位置一致地出现，证明了m6dA的同质性。我们进一步表明，这是第一次，在一条染色体内更高水平的m6dA同质性。大多数m6dA存在于来自二倍体样本的一条染色体上，表明存在遗传。我们的转录组分析不仅表明具有m6dA的人类基因与较高的RNA转录水平相关，而且鉴定出具有单倍型特异性m6dA甲基化的等位基因特异性基因转录物，这与不同的生物学功能有关。我们的分析证明了m6dA标记在人类基因组中出现的准确性和一致性，这表明m6dA标记在人类中是精确遗传的。
A novel DNA modification, N-6 methylated deoxyadenosine (m6dA), has recently been discovered in eukaryotic genomes. Despite its low abundance in eukaryotes, m6dA is implicated in human diseases such as cancer. It is therefore important to precisely identify and characterize m6dA in the human genome. Here, we identify m6dA sites at nucleotide level, in different human cells, genome wide. We compare m6dA features between distinct human cells and identify m6dA characteristics in human genomes. Our data demonstrates for the first time that despite low m6dA abundance, the m6dA mark does often occur consistently at the same genomic location within a given human cell type, demonstrating m6dA homogeneity. We further show, for the first time, higher levels of m6dA homogeneity within one chromosome. Most m6dA are found on a single chromosome from a diploid sample, suggesting inheritance. Our transcriptome analysis not only indicates that human genes with m6dA are associated with higher RNA transcript levels but identifies allele-specific gene transcripts showing haplotype-specific m6dA methylation, which are implicated in different biological functions. Our analyses demonstrate the precision and consistency by which the m6dA mark occurs within the human genome, suggesting that m6dA marks are precisely inherited in humans.