A novel N^(6)-Deoxyadenine methyltransferase METL-9 modulates C.elegans immunity via dichotomous mechanisms

查看全文 作　　者：Chengchuan [1,2,3,4]Ma;Tingling [1,2]Xue;Qi [5]Peng;Jie [5]Zhang;Jialiang [1,6]Guan;Wanqiu [5]Ding;Yi [1,2]Li;Peixue [1,2]Xia;Liankui [1,2]Zhou;Tianyu [1]Zhao;Sheng [7]Wang;Li [1]Quan;Chuan-Yun [5]Li;Ying [1,2,3]Liu 机构地区：[1]State Key Laboratory of Membrane Biology,New Cornerstone Science Laboratory,Institute of Molecular Medicine,College of Future Technology,Peking University,Beijing,China;[2]Peking-Tsinghua Center for Life Sciences,Peking University,Beijing,China;[3]Beijing Advanced Innovation Center for Genomics,Beijing,China;[4]Research Center for Stem Cell and Regenerative Medicine,Institute of Blood Transfusion,Chinese Academy of Medical Sciences and Peking Union Medical College,Chengdu,Sichuan,China;[5]Laboratory of Bioinformatics and Genomic Medicine,Institute of Molecular Medicine,College of Future Technology,Peking University,Beijing,China;[6]PKU-Tsinghua-NIBS Graduate Program,Academy for Advanced Interdisciplinary Studies,Peking University,Beijing,China;[7]Shanghai Zelixir Biotech Company Ltd.,Shanghai,China 出　　处：《Cell Research》索引2023年第33卷第8期,共12页 基　　金：the Tencent Foundation through the XPLORER PRIZE.Y.Liu was supported by grants from the National Natural Science Foundation of China(31925012);the HHMI International Research Scholar Program(55008739);C.M.was supported by grants from the National Natural Science Foundation of China(31900425);China Postdoctoral Science Foundation(2019T120015)and Postdoctoral Foundation of Peking-Tsinghua Center for Life Sciences. 摘　　要：N_(6)-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. 关 键 词：C.elegans IMMUNITY ADENINE