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CDYL suppresses epileptogenesis in mice through repression of axonal Nav1.6 sodium channel expression

Author

Listed:
  • Yongqing Liu

    (Peking University Health Science Center
    Peking University Health Science Center)

  • Shirong Lai

    (Peking University Health Science Center
    Peking University Health Science Center)

  • Weining Ma

    (Shengjing Hospital Affiliated to China Medical University)

  • Wei Ke

    (Beijing Normal University)

  • Chan Zhang

    (Peking University Health Science Center)

  • Shumeng Liu

    (Peking University Health Science Center)

  • Yu Zhang

    (Peking University Health Science Center)

  • Fei Pei

    (Peking University Health Science Center)

  • Shaoyi Li

    (Shengjing Hospital Affiliated to China Medical University)

  • Ming Yi

    (Peking University Health Science Center)

  • Yousheng Shu

    (Beijing Normal University)

  • Yongfeng Shang

    (Peking University Health Science Center
    Capital Medical University
    Tianjin Medical University)

  • Jing Liang

    (Peking University Health Science Center)

  • Zhuo Huang

    (Peking University Health Science Center
    Peking University Health Science Center
    State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences)

Abstract

Impairment of intrinsic plasticity is involved in a range of neurological disorders such as epilepsy. However, how intrinsic excitability is regulated is still not fully understood. Here we report that the epigenetic factor Chromodomain Y-like (CDYL) protein is a critical regulator of the initiation and maintenance of intrinsic neuroplasticity by regulating voltage-gated ion channels in mouse brains. CDYL binds to a regulatory element in the intron region of SCN8A and mainly recruits H3K27me3 activity for transcriptional repression of the gene. Knockdown of CDYL in hippocampal neurons results in augmented Nav1.6 currents, lower neuronal threshold, and increased seizure susceptibility, whereas transgenic mice over-expressing CDYL exhibit higher neuronal threshold and are less prone to epileptogenesis. Finally, examination of human brain tissues reveals decreased CDYL and increased SCN8A in the temporal lobe epilepsy group. Together, our findings indicate CDYL is a critical player for experience-dependent gene regulation in controlling intrinsic excitability.

Suggested Citation

  • Yongqing Liu & Shirong Lai & Weining Ma & Wei Ke & Chan Zhang & Shumeng Liu & Yu Zhang & Fei Pei & Shaoyi Li & Ming Yi & Yousheng Shu & Yongfeng Shang & Jing Liang & Zhuo Huang, 2017. "CDYL suppresses epileptogenesis in mice through repression of axonal Nav1.6 sodium channel expression," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00368-z
    DOI: 10.1038/s41467-017-00368-z
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    Cited by:

    1. Yiwei Gao & Shuai Xu & Xiaoli Cui & Hao Xu & Yunlong Qiu & Yiqing Wei & Yanli Dong & Boling Zhu & Chao Peng & Shiqi Liu & Xuejun Cai Zhang & Jianyuan Sun & Zhuo Huang & Yan Zhao, 2023. "Molecular insights into the gating mechanisms of voltage-gated calcium channel CaV2.3," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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