Volume 33, No 8, Aug 2023

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 33 Issue 8, August 2023: 628-639   |  Open Access

ORIGINAL ARTICLES

A novel N⁶-Deoxyadenine methyltransferase METL-9 modulates C. elegans immunity via dichotomous mechanisms

Chengchuan Ma^{1,2,3,4,†,*} , Tingling Xue^1,2,† , Qi Peng^5,† , Jie Zhang⁵ , Jialiang Guan^1,6 , Wanqiu Ding⁵ , Yi Li^1,2 , Peixue Xia^1,2 , Liankui Zhou^1,2 , Tianyu Zhao¹ , Sheng Wang⁷ , Li Quan¹ , Chuan-Yun Li^5,* , Ying Liu^1,2,3,*

¹State Key Laboratory of Membrane Biology, New Cornerstone Science Laboratory, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China
²Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
³Beijing Advanced Innovation Center for Genomics, Beijing, China
⁴Research Center for Stem Cell and Regenerative Medicine, Institute of Blood Transfusion, Chengdu, Sichuan, China
⁵Laboratory of Bioinformatics and Genomic Medicine, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China
⁶PKU-Tsinghua-NIBS Graduate Program, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
⁷Shanghai Zelixir Biotech Company Ltd., Shanghai, China
^†These authors contributed equally: Chengchuan Ma, Tingling Xue, Qi Peng
Correspondence: Chengchuan Ma(ma.cc@ibt.pumc.edu.cn)Chuan-Yun Li(chuanyunli@pku.edu.cn)Ying Liu(ying.liu@pku.edu.cn)

N6-Methyldeoxyadenine (6mA) has been rediscovered as a DNA modification with potential biological function in metazoans. However, the physiological function and regulatory mechanisms regarding the establishment, maintenance and removal of 6mA in eukaryotes are still poorly understood. Here we show that genomic 6mA levels change in response to pathogenic infection in Caenorhabditis elegans (C. elegans). We further identify METL-9 as the methyltransferase that catalyzes DNA 6mA modifications upon pathogen infection. Deficiency of METL-9 impairs the induction of innate immune response genes and renders the animals more susceptible to pathogen infection. Interestingly, METL-9 functions through both 6mA-dependent and -independent mechanisms to transcriptionally regulate innate immunity. Our findings reveal that 6mA is a functional DNA modification in immunomodulation in C. elegans.

https://doi.org/10.1038/s41422-023-00826-y

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