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

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العنوان: CDYL suppresses epileptogenesis in mice through repression of axonal Nav1.6 sodium channel expression
المؤلفون: Liu, Yongqing, Lai, Shirong, Ma, Weining, Ke, Wei, Zhang, Chan, Liu, Shumeng, Zhang, Yu, Pei, Fei, Li, Shaoyi, Yi, Ming, Shu, Yousheng, Shang, Yongfeng, Liang, Jing, Huang, Zhuo
المساهمون: Liang, J, Huang, Z (reprint author), Peking Univ, Key Lab Carcinogenesis & Translat Res,Minist Educ, State Key Lab Nat & Biomimet Drugs, Beijing Key Lab Prot Posttranslat Modificat & Cel, Beijing 100191, Peoples R China., Huang, Z (reprint author), Peking Univ, Hlth Sci Ctr, Dept Mol & Cellular Pharmacol, Sch Pharmaceut Sci, Beijing 100191, Peoples R China., Peking Univ, Key Lab Carcinogenesis & Translat Res,Minist Educ, State Key Lab Nat & Biomimet Drugs, Beijing Key Lab Prot Posttranslat Modificat & Cel, Beijing 100191, Peoples R China., Peking Univ, Hlth Sci Ctr, Dept Mol & Cellular Pharmacol, Sch Pharmaceut Sci, Beijing 100191, Peoples R China., China Med Univ, Dept Neurol, Shengjing Hosp, Shenyang 110000, Liaoning, Peoples R China., Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China., Beijing Normal Univ, IDG McGovern Inst Brain Res, Sch Brain & Cognit Sci, Collaborat Innovat Ctr Brain Sci, Beijing 100875, Peoples R China., Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Beijing 100191, Peoples R China., Peking Univ, Hlth Sci Ctr, Dept Neurobiol, Beijing 100191, Peoples R China., Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100191, Peoples R China., Capital Med Univ, Dept Biochem & Mol Biol, Sch Basic Med Sci, Beijing 100069, Peoples R China., Tianjin Med Univ, Dept Biochem & Mol Biol, Tianjin 300070, Peoples R China., Chinese Acad Sci, State Key Lab Organometall Chem, Shanghai 200032, Peoples R China.
المصدر: SCI
بيانات النشر: NATURE COMMUNICATIONS
سنة النشر: 2017
المجموعة: Peking University Institutional Repository (PKU IR) / 北京大学机构知识库
مصطلحات موضوعية: PRESYNAPTIC HCN1 CHANNELS, NEURONAL HYPEREXCITABILITY, EPIGENETIC REGULATION, STATUS EPILEPTICUS, STEM-CELLS, PLASTICITY, EXCITABILITY, EPILEPSY, TRANSCRIPTION, GENERATION
الوصف: 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. ; 973 Program from the Ministry of Science and Technology of China [2015CB559200, 2014CB542004]; National Natural Science Foundation of China [81572771, 31371301, 81371432, 91219201, 81130048] ; SCI(E) ; ARTICLE ; 8
نوع الوثيقة: journal/newspaper
اللغة: English
تدمد: 2041-1723
العلاقة: NATURE COMMUNICATIONS.2017,8.; 1905451; http://hdl.handle.net/20.500.11897/471380Test; WOS:000408376900003
DOI: 10.1038/s41467-017-00368-z
الإتاحة: https://doi.org/20.500.11897/471380Test
https://doi.org/10.1038/s41467-017-00368-zTest
https://hdl.handle.net/20.500.11897/471380Test
رقم الانضمام: edsbas.2C72CFCF
قاعدة البيانات: BASE
الوصف
تدمد:20411723
DOI:10.1038/s41467-017-00368-z