Wang Yuanyuan, Nan Bei, Ye Fei, Zhang Zhe, Yang Wentao, Pan Bo, Wei Fan, Duan Lili, Li Haicheng, Niu Junhua, Ju Aili, Liu Yongqiang, Wang Dantong, Zhang Wenxin, Liu Yifan, Gao Shan
Key Laboratory of Evolution & Marine Biodiversity (Ministry of Education) and Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China.
Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao 266237, China.
Proc Natl Acad Sci U S A. 2025 Jan 21;122(3):e2413037121. doi: 10.1073/pnas.2413037121. Epub 2025 Jan 15.
Stable inheritance of DNA N-methyladenine (6mA) is crucial for its biological functions in eukaryotes. Here, we identify two distinct methyltransferase (MTase) complexes, both sharing the catalytic subunit AMT1, but featuring AMT6 and AMT7 as their unique components, respectively. While the two complexes are jointly responsible for 6mA maintenance methylation, they exhibit distinct enzymology, DNA/chromatin affinity, genomic distribution, and knockout phenotypes. AMT7 complex, featuring high MTase activity and processivity, is connected to transcription-associated epigenetic marks, including H2A.Z and H3K4me3, and is required for the bulk of maintenance methylation. In contrast, AMT6 complex, with reduced activity and processivity, is recruited by PCNA to initiate maintenance methylation immediately after DNA replication. These two complexes coordinate in maintenance methylation. By integrating signals from both replication and transcription, this mechanism ensures the faithful and efficient transmission of 6mA as an epigenetic mark in eukaryotes.
DNA N-甲基腺嘌呤（6mA）的稳定遗传对其在真核生物中的生物学功能至关重要。在此，我们鉴定出两种不同的甲基转移酶（MTase）复合物，它们都共享催化亚基AMT1，但分别以AMT6和AMT7作为其独特组分。虽然这两种复合物共同负责6mA的维持甲基化，但它们表现出不同的酶学性质、DNA/染色质亲和力、基因组分布和敲除表型。具有高MTase活性和持续合成能力的AMT7复合物与转录相关的表观遗传标记（包括H2A.Z和H3K4me3）相关联，并且是大部分维持甲基化所必需的。相比之下，活性和持续合成能力降低的AMT6复合物被PCNA招募，在DNA复制后立即启动维持甲基化。这两种复合物在维持甲基化过程中相互协调。通过整合来自复制和转录的信号，这种机制确保了6mA作为真核生物表观遗传标记的忠实和有效传递。
