N6-methyladenine DNA modification modulates pathogen virulence in nematodes
Abstract
Understanding the global regulatory mechanisms that control pathogen virulence gene expression is essential for elucidating the molecular basis of pathogenicity. N6-methyladenine (6 mA) plays a crucial role in regulating gene expression in response to various environmental stresses; however, its role in pathogen virulence remains largely unexplored. Here, we report the widespread occurrence of 6 mA across 17 nematode isolates and map its genomic landscape in six notorious agriculturally important pathogen root-knot nematodes (RKNs). We demonstrated that 6 mA is characterized by a conserved GAG motif across nematodes, but exhibits species-specific distribution patterns and distinct effects on gene expression. In particular, its enrichment in transposable elements (TEs) differs between polyploid and diploid nematodes, suggesting lineage-specific epigenetic regulation potentially associated with polyploidy. We further identified two functional 6 mA demethylases, MiNMAD-1 and MiNMAD-2, and confirmed their catalytic activity and active sites. Host-induced gene silencing (HIGS) of minmad-1 significantly increased plant resistance to three polyploid RKN species. A detailed functional analysis revealed that minmad-1 knockdown broadly affected gene expression during the parasitic stage, including genes involved in virulence, thereby reducing nematode infectivity. Together, our findings suggest 6 mA demethylase as a key epigenetic regulator of RKNs’ virulence, providing new insights into nematode biology and offering promising targets for the development of sustainable control strategies.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (18)
Dadong Dai
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University
Shurong Zhang
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University
Boyan Hu
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University
Yayi Zhou
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University
Simeng Cui
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University
Jia Sun
National Medical Products Administration Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University
Yali Zhang
Xueyu Wang
College of Sciences
Shahid Siddique
Department of Entomology and Nematology, University of California
Dexin Bo
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University
Min Zhang
Valerie M. Williamson
Department of Plant Pathology, University of California
Haozhe Yao
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University
Xinya Duan
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University
Wentao Wu
Donghai Peng
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University
Jinshui Zheng
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University
Ming Sun