北京大学Ying Liu，Chuan-Yun Li和Chengchuan Ma共同合作，近期取得重要工作进展。他们研究发现新型N⁶-脱氧腺嘌呤甲基转移酶METL-9通过二分机制调节秀丽隐杆线虫（C.elegans）的免疫。相关研究成果2023年6月5日在线发表于《细胞研究》杂志上。

据介绍，N⁶-甲基脱氧腺嘌呤（6mA）作为一种具有潜在生物学功能的DNA修饰在后生动物中被重新发现。然而，人们对于真核生物中6mA的建立、维持和去除的生理功能及调节机制仍知之甚少。

研究人员发现，基因组6mA水平在C.elegans的致病性感染反应中发生变化。研究人员进一步鉴定METL-9是在病原体感染时催化DNA 6mA修饰的甲基转移酶。METL-9的缺乏削弱了先天免疫反应基因的诱导，并使动物更容易受到病原体感染。METL-9通过6mA依赖性和非依赖性机制发挥作用，转录调节先天免疫。

总之，这一研究结果表明，6mA是C.elegans免疫调节中的一种功能性DNA修饰。

附：英文原文

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

Author: Ma, Chengchuan, Xue, Tingling, Peng, Qi, Zhang, Jie, Guan, Jialiang, Ding, Wanqiu, Li, Yi, Xia, Peixue, Zhou, Liankui, Zhao, Tianyu, Wang, Sheng, Quan, Li, Li, Chuan-Yun, Liu, Ying

Issue&Volume: 2023-06-05

Abstract: 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.

DOI: 10.1038/s41422-023-00826-y

Source: https://www.nature.com/articles/s41422-023-00826-y