伦敦玛丽女王大学Alex de Mendoza团队近日取得一项新成果。经过不懈努力，他们开发出与转录允许染色质相关的腺嘌呤DNA甲基化在真核生物中广泛存在。2025年11月18日出版的《自然—遗传学》发表了这项成果。

在这里，该团队应用牛津纳米孔测序对18种单细胞真核生物的6mA碱基对分辨率进行分析，这些生物代表了所有主要的超群。该课题组发现稳健的6mA模式只发生在编码腺嘌呤甲基转移酶AMT1的物种中。值得注意的是，6mA持续积累在转录起始位点下游，位于H3K4me3标记的核小体之间，表明其与转录激活的保守关联。他们的研究结果支持了这样一种观点，即最后的真核生物共同祖先具有双甲基化系统，具有转录相关的6mA和抑制性5mC，这在多细胞和单细胞谱系中都通过AMT1途径的缺失而被反复简化。

据介绍，DNA甲基化是真核生物基因组的关键调控因子，最常见的是通过5-甲基胞嘧啶（5mC）进行。相比之下，N⁶ -甲基腺嘌呤（6mA）在真核生物中的存在和功能一直存在争议，由于方法学上的伪像而产生了相互矛盾的报告。然而，一些单细胞谱系，包括纤毛虫、早期分支真菌和藻类衣藻，显示出明显的6mA信号，这引发了关于它们的起源和进化作用的问题。

附：英文原文

Title: Adenine DNA methylation associated with transcriptionally permissive chromatin is widespread across eukaryotes

Author: Romero Charria, Pedro, Navarrete, Cristina, Ovchinnikov, Vladimir, Xu, Lan, Sarre, Luke A., Shabardina, Victoria, Ksiezopolska, Ewa, Casacuberta, Elena, Lara-Astiaso, David, Seb-Pedrs, Arnau, de Mendoza, Alex

Issue&Volume: 2025-11-18

Abstract: DNA methylation is a key regulator of eukaryotic genomes, most commonly through 5-methylcytosine (5mC). In contrast, the existence and function of N6-methyladenine (6mA) in eukaryotes have been controversial, with conflicting reports resulting from methodological artifacts. Nevertheless, some unicellular lineages, including ciliates, early-branching fungi and the alga Chlamydomonas, show robust 6mA signals, raising questions about their origin and evolutionary role. Here we apply Oxford Nanopore sequencing to profile 6mA at base-pair resolution across 18 unicellular eukaryotes representing all major supergroups. We find that robust 6mA patterns occur only in species that encode the adenine methyltransferase AMT1. Notably, 6mA consistently accumulates downstream of transcriptional start sites, positioned between H3K4me3-marked nucleosomes, indicating a conserved association with transcriptional activation. Our results support the idea that the last eukaryotic common ancestor had a dual methylation system, with transcription-linked 6mA and repressive 5mC, which has been repeatedly simplified in both multicellular and unicellular lineages through the loss of the AMT1 pathway.

DOI: 10.1038/s41588-025-02409-6

Source: https://www.nature.com/articles/s41588-025-02409-6