Widespread adenine N6-methylation of active genes in fungi

Widespread adenine N6-methylation of active genes in fungi
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DOI:
10.1038/ng.3859
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发表时间:
2017-06-01
期刊:
影响因子:
30.8
通讯作者:
Grigoriev, Igor V.
Grigoriev, Igor V.
中科院分区:
生物学1区
文献类型:
--
作者:
Mondo, Stephen J.;Dannebaum, Richard O.;Grigoriev, Igor V.

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N6-甲基脱氧腺嘌呤(6 MA)是一种非规范的DNA碱基修饰,存在于植物和动物基因组中(1-4),但它在其他真核生物中的流行情况及其与基因组功能的关系尚不清楚。在这里,我们报告了在早期分化的真菌谱系中,丰富的6 mA与转录活性基因相关(5)。利用对16种不同真菌基因组的单分子长阅读测序,我们观察到在早期分化的真菌中,高达2.8%的腺嘌呤被甲基化,远远超过在其他真核生物和更多的衍生真菌中观察到的水平。6 mA在APT二核苷酸上呈对称性分布,集中在表达基因转录起始点周围致密的甲基化腺嘌呤簇中,其分布与5-甲基胞嘧啶呈负相关。我们的结果显示,6 mA和5-甲基胞嘧啶的基因组分布有明显的差异,并加强了6 mA作为基因表达相关的表观基因组标记在真核生物中的独特作用。
N6-methyldeoxyadenine (6mA) is a noncanonical DNA base modification present at low levels in plant and animal genomes(1-4), but its prevalence and association with genome function in other eukaryotic lineages remains poorly understood. Here we report that abundant 6mA is associated with transcriptionally active genes in early-diverging fungal lineages(5). Using single-molecule long-read sequencing of 16 diverse fungal genomes, we observed that up to 2.8% of all adenines were methylated in early-diverging fungi, far exceeding levels observed in other eukaryotes and more derived fungi. 6mA occurred symmetrically at ApT dinucleotides and was concentrated in dense methylated adenine clusters surrounding the transcriptional start sites of expressed genes; its distribution was inversely correlated with that of 5-methylcytosine. Our results show a striking contrast in the genomic distributions of 6mA and 5-methylcytosine and reinforce a distinct role for 6mA as a gene-expression-associated epigenomic mark in eukaryotes.