Dual modes of DNA N <sup>6</sup> -methyladenine maintenance by distinct methyltransferase complexes
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (16)
Yuanyuan Wang
Bei Nan
Key Laboratory of Evolution & Marine Biodiversity (Ministry of Education) and Institute of Evolution & Marine Biodiversity, Ocean University of China
Fei Ye
Zhe Zhang
Wentao Yang
Department of Biochemistry & Molecular Medicine, University of Southern California Keck School of Medicine
Bo Pan
Fan Wei
Lili Duan
Key Laboratory of Evolution & Marine Biodiversity (Ministry of Education) and Institute of Evolution & Marine Biodiversity, Ocean University of China
Haicheng Li
Center for Flexible Electronics Technology, Tsinghua University, No. 30, Shuangqing Road, Beijing 100084, People’s Republic of China
Junhua Niu
Key Laboratory of Evolution & Marine Biodiversity (Ministry of Education) and Institute of Evolution & Marine Biodiversity, Ocean University of China
Aili Ju
Key Laboratory of Evolution & Marine Biodiversity (Ministry of Education) and Institute of Evolution & Marine Biodiversity, Ocean University of China
Yongqiang Liu
Key Laboratory of Evolution & Marine Biodiversity (Ministry of Education) and Institute of Evolution & Marine Biodiversity, Ocean University of China
Dantong Wang
BGI Research
Wenxin Zhang
Institute of Biomedical Research, Yunnan University
Yifan Liu
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering
Shan Gao