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Cited by 1Nematode management and characterization studiesEpigenetics and DNA MethylationHelminth infection and control

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N6-methyladenine DNA modification modulates pathogen virulence in nematodes

Open access
Dai, Dadong, Zhang, Shurong, Hu, Boyan, Zhou, Yayi, Cui, Simeng, Sun, Jia, Zhang, Yali, Wang, Xueyu, Siddique, Shahid, Bo, Dexin, Zhang, Min, Williamson, Valerie M., Yao, Haozhe, Duan, Xinya, Wu, Wentao, Peng, Donghai, Zheng, Jinshui, Sun, Ming·2026·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2525035123

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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.

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Metadata

Authors
Dai, D., Zhang, S., Hu, B., Zhou, Y., Cui, S., Sun, J., Zhang, Y., Wang, X., Siddique, S., Bo, D., Zhang, M., Williamson, V. M., Yao, H., Duan, X., Wu, W., Peng, D., Zheng, J., & Sun, M.
Affiliations
  • Huazhong Agricultural University (CN)
  • University of California System (US)
  • Wuhan Academy of Agricultural Sciences (CN)
  • Yunnan Agricultural University (CN)
Corresponding author
  • Dai, Dadong
  • Zhang, Shurong
  • Zheng, Jinshui
  • Sun, Ming
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2026-03-04
Volume
123
Issue
10
Pages
e2525035123-e2525035123
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2525035123
OpenAlex
W7133551589
Cited by
1
References
2
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • MOST | National Natural Science Foundation of China (U20A2040, 31970076)
  • MOST | National Key Research and Development Program of China (2017YFD0201201)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Nematode management and characterization studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Immunology and Microbiology › Parasitology › Helminth infection and control
Keywords
N6-methyladenine, DNA methylation, root-knot nematode, nematode virulence, epigenetic regulation, transposable elements, polyploidy, demethylases, host-induced gene silencing, plant resistance, gene expression regulation
MeSH terms
Adenine, Animals, DNA Transposable Elements, Nematoda, Plant Diseases, Tylenchoidea, Virulence, Helminth Proteins, DNA Methylation, Gene Silencing, Epigenesis, Genetic

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