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Single amino acid mutations in histone H3.3 illuminate the functional significance of H3K4 methylation in plants

Author

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  • Mande Xue

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Duke University Medical Centre)

  • Lijun Ma

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Shandong University)

  • Xiaoyi Li

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    National University of Singapore)

  • Huairen Zhang

    (Chinese Academy of Sciences)

  • Fengyue Zhao

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Qian Liu

    (National University of Singapore)

  • Danhua Jiang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    National University of Singapore)

Abstract

Although histone modifications are linked with chromatin activities such as transcription, proofs of their causal importance remain limited. Sequence variants within each histone family expand chromatin diversity and may carry specific modifications, further raising questions about their coordination. Here, we investigate the role of lysine 4 (K4) in two Arabidopsis H3 variants, H3.1 and H3.3. K4 is essential for H3.3 function but not H3.1 in plant development. Mutating K4 in H3.3 drastically reduced H3K4 methylation levels and mimicked the transcriptomic effects of losing SDG2, the major H3K4 trimethylation (H3K4me3) methyltransferase. Moreover, H3.3K4 and SDG2 are required for de novo gene activation and RNA Pol II elongation. H3K4 methylation is preferentially enriched on H3.3, likely due to the coordinated activity of H3.3 deposition and H3K4 methylation. Furthermore, we reveal the diverse impacts of K4 nearby residue mutations on H3K4 methylation and H3.3 function. These findings highlight H3.3 as a critical substrate for H3K4 methylation, which is important for gene expression regulation.

Suggested Citation

  • Mande Xue & Lijun Ma & Xiaoyi Li & Huairen Zhang & Fengyue Zhao & Qian Liu & Danhua Jiang, 2025. "Single amino acid mutations in histone H3.3 illuminate the functional significance of H3K4 methylation in plants," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59711-4
    DOI: 10.1038/s41467-025-59711-4
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