Dual modes of DNA N 6 -methyladenine maintenance by distinct methyltransferase complexes

IF 9.4 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-01-15 DOI:10.1073/pnas.2413037121

Yuanyuan Wang, Bei Nan, Fei Ye, Zhe Zhang, Wentao Yang, Bo Pan, Fan Wei, Lili Duan, Haicheng Li, Junhua Niu, Aili Ju, Yongqiang Liu, Dantong Wang, Wenxin Zhang, Yifan Liu, Shan Gao

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引用次数: 0

Abstract

Stable inheritance of DNA N 6 -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.

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不同甲基转移酶复合物维持DNA n6 -甲基腺嘌呤的双重模式

DNA n6 -甲基腺嘌呤（n6 - methylladenine, 6mA）的稳定遗传对其在真核生物中的生物学功能至关重要。在这里，我们鉴定了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为其独特组分。虽然这两个复合物共同负责6mA维持甲基化，但它们表现出不同的酶学、DNA/染色质亲和力、基因组分布和敲除表型。AMT7复合体具有高MTase活性和加工性，与转录相关的表观遗传标记（包括H2A）有关。Z和H3K4me3，并且是维持甲基化所需的大部分。相比之下，活性和加工性降低的AMT6复合体被PCNA招募，在DNA复制后立即启动维持性甲基化。这两个复合物在维持甲基化过程中相互配合。通过整合来自复制和转录的信号，该机制确保了6mA作为表观遗传标记在真核生物中忠实有效的传递。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Proceedings of the National Academy of Sciences of the United States of America 综合性期刊-综合性期刊

CiteScore

19.00

自引率

0.90%

发文量

3575

审稿时长

2.5 months

期刊介绍： The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.