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

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 () and Zhuo Huang ()
Additional contact information
Yongqing Liu: Peking University Health Science Center
Shirong Lai: 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
Jing Liang: Peking University Health Science Center
Zhuo Huang: Peking University Health Science Center

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-00368-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00368-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-00368-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().