Dual Modes of DNA N-methyladenine Maintenance by Distinct Methyltransferase Complexes

Overview

Journal Proc Natl Acad Sci U S A

Date 2025 Jan 15

PMID 39813249

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

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