Identification of a somatic H3K23me3 methyltransferase SET-19 in C. elegans

Xu, M.; Fan, Z.; Yan, C.; Chen, X.; Huang, X.; Zhu, C.; Hong, M.; Cheng, J.; Hou, X.; Li, S.; Li, M.; Shi, Y.; Huang, M.; Guang, S.; Feng, X.

doi:10.64898/2026.03.24.713969

bioRxiv · 10.64898/2026.03.24.713969

Identification of a somatic H3K23me3 methyltransferase SET-19 in C. elegans

Xu, M.·Fan, Z.·Yan, C.·Chen, X.·Huang, X.·Zhu, C.·Hong, M.·Cheng, J.·Hou, X.·Li, S.·Li, M.·Shi, Y.·Huang, M.·Guang, S.·Feng, X.

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Abstract

Histone methylation plays essential roles in modulating chromatin organization and gene expression. H3K23 methylation is a conserved histone modification, yet its biological roles and the enzymes responsible for its deposition remain poorly understood. Here, we show that the loss of set-19 leads to a pronounced reduction in H3K23 methylation in C. elegans, as revealed by quantitative mass spectrometry, western blotting, and immunofluorescence staining. In vitro biochemical assays show that recombinant SET-19 proteins purified from E. coli directly catalyze H3K23 methylation. Genome-wide chromatin immunoprecipitation assays reveal that H3K23me3 is enriched at heterochromatic regions and that loss of set-19 alters H3K23me3 levels, accompanied by derepression of gene expression. Genetic analyses indicate that SET-19 is dispensable for both germline and somatic RNAi as well as transgenerational epigenetic inheritance of RNAi. SET-19 is predominantly expressed in somatic cells and specifically mediates H3K23me3 deposition in somatic tissues. The loss of set-19 causes a developmental delay without affecting fertility. Together, our results identify SET-19 as a somatic H3K23 methyltransferase and link H3K23me3 to gene repression in C. elegans.

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Xu, M., Fan, Z., Yan, C., Chen, X., Huang, X., Zhu, C., Hong, M., Cheng, J., Hou, X., Li, S., Li, M., Shi, Y., Huang, M., Guang, S., Feng, X.. 2026-03-26. Identification of a somatic H3K23me3 methyltransferase SET-19 in C. elegans. https://doi.org/10.64898/2026.03.24.713969

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