CDYL suppresses epileptogenesis in mice through repression of axonal Nav1.6 sodium channel expression.
CDYL suppresses epileptogenesis in mice through repression of axonal Nav1.6 sodium channel expression.
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CDYL 通过抑制轴突 Nav1.6 钠通道表达来抑制小鼠癫痫发生。
DOI：
10.1038/s41467-017-00368-z
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发表时间：
2017-08-25
影响因子：
16.6
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Liu Y;Lai S;Ma W;Ke W;Zhang C;Liu S;Zhang Y;Pei F;Li S;Yi M;Shu Y;Shang Y;Liang J;Huang Z
内在可塑性的损伤涉及一系列神经系统疾病，如癫痫。然而，内在兴奋性是如何调节的仍然没有完全理解。在这里，我们报告，表观遗传因子染色体Y样（CDYL）蛋白是一个重要的调节器的启动和维持内在的神经可塑性，通过调节电压门控离子通道在小鼠大脑。CDYL与SCN 8A内含子区的调控元件结合，主要募集H3K27me3活性以抑制基因的转录。在海马神经元中敲低CDYL导致增强的Nav1.6电流、较低的神经元阈值和增加的癫痫发作易感性，而过表达CDYL的转基因小鼠表现出较高的神经元阈值并且不易于癫痫发生。最后，对人脑组织的检查揭示了颞叶癫痫组中CDYL减少和SCN 8A增加。总之，我们的研究结果表明，CDYL是控制内在兴奋性的经验依赖性基因调控的关键球员。
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.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
15.9
作者：
Krashes, Michael J.;Koda, Shuichi;Lowell, Bradford B.
通讯作者：
Lowell, Bradford B.
DOI：
10.1523/jneurosci.1531-09.2009
发表时间：
2009-09-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Huang Z;Walker MC;Shah MM
通讯作者：
Shah MM
影响因子：
7.7
作者：
Caron, C;Pivot-Pajot, C;Khochbin, S
通讯作者：
Khochbin, S
影响因子：
5.3
作者：
Hamada, Mustafa S.;Kole, Maarten H. P.
通讯作者：
Kole, Maarten H. P.