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SMYD5 catalyzes histone H3 lysine 36 trimethylation at promoters

Author

Listed:
  • Yanjun Zhang

    (Zhejiang University)

  • Yuan Fang

    (Zhejiang University)

  • Yin Tang

    (Zhejiang University)

  • Shixun Han

    (Zhejiang University)

  • Junqi Jia

    (Zhejiang University)

  • Xinyi Wan

    (Zhejiang University)

  • Jiaqi Chen

    (Zhejiang University School of Medicine)

  • Ying Yuan

    (Zhejiang University School of Medicine)

  • Bin Zhao

    (Zhejiang University)

  • Dong Fang

    (Zhejiang University
    Zhejiang University School of Medicine)

Abstract

Histone marks, carriers of epigenetic information, regulate gene expression. In mammalian cells, H3K36me3 is mainly catalyzed by SETD2 at gene body regions. Here, we find that in addition to gene body regions, H3K36me3 is enriched at promoters in primary cells. Through screening, we identify SMYD5, which is recruited to chromatin by RNA polymerase II, as a methyltransferase catalyzing H3K36me3 at promoters. The enzymatic activity of SMYD5 is dependent on its C-terminal glutamic acid-rich domain. Overexpression of full-length Smyd5, but not the C-terminal domain-truncated Smyd5, restores H3K36me3 at promoters in Smyd5 knockout cells. Furthermore, elevated Smyd5 expression contributes to tumorigenesis in liver hepatocellular carcinoma. Together, our findings identify SMYD5 as the H3K36me3 methyltransferase at promoters that regulates gene expression, providing insights into the localization and function of H3K36me3.

Suggested Citation

  • Yanjun Zhang & Yuan Fang & Yin Tang & Shixun Han & Junqi Jia & Xinyi Wan & Jiaqi Chen & Ying Yuan & Bin Zhao & Dong Fang, 2022. "SMYD5 catalyzes histone H3 lysine 36 trimethylation at promoters," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30940-1
    DOI: 10.1038/s41467-022-30940-1
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    References listed on IDEAS

    as
    1. Huilin Huang & Hengyou Weng & Keren Zhou & Tong Wu & Boxuan Simen Zhao & Mingli Sun & Zhenhua Chen & Xiaolan Deng & Gang Xiao & Franziska Auer & Lars Klemm & Huizhe Wu & Zhixiang Zuo & Xi Qin & Yunzhu, 2019. "Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally," Nature, Nature, vol. 567(7748), pages 414-419, March.
    2. Hong Wen & Yuanyuan Li & Yuanxin Xi & Shiming Jiang & Sabrina Stratton & Danni Peng & Kaori Tanaka & Yongfeng Ren & Zheng Xia & Jun Wu & Bing Li & Michelle C. Barton & Wei Li & Haitao Li & Xiaobing Sh, 2014. "ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression," Nature, Nature, vol. 508(7495), pages 263-268, April.
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