Nature communications, 2017-08, Vol.8 (1), p.355-17, Article 355
2017
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- Autor(en) / Beteiligte
- Titel
- CDYL suppresses epileptogenesis in mice through repression of axonal Nav1.6 sodium channel expression
- Ist Teil von
- Nature communications, 2017-08, Vol.8 (1), p.355-17, Article 355
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. Alterations in intrinsic plasticity are important in epilepsy. Here the authors show that the epigenetic factor CDYL regulates the gene expression of the voltage gated sodium channel, Nav1.6, which contributes to seizures in a rat model of epilepsy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-017-00368-zTitel-ID: cdi_doaj_primary_oai_doaj_org_article_c1fec91be8b04fc981937dd1ca6abdea
- Format
- –
- Schlagworte
- 631/378/1689/178, 631/378/2584/1695, Animals, Axonal plasticity, Co-Repressor Proteins - genetics, Co-Repressor Proteins - metabolism, Co-Repressor Proteins - physiology, Epilepsy, Epilepsy - genetics, Epilepsy - metabolism, Gene expression, Gene Expression Regulation, Gene Knockdown Techniques, Hippocampus - metabolism, Hippocampus - pathology, Histone Acetyltransferases - genetics, Histone Acetyltransferases - metabolism, Histone Acetyltransferases - physiology, Humanities and Social Sciences, Humans, Ion Channel Gating - genetics, Male, Mice, Inbred C57BL, Mice, Transgenic, multidisciplinary, NAV1.6 Voltage-Gated Sodium Channel - metabolism, Neuronal Plasticity - genetics, Rats, Sprague-Dawley, Science, Science (multidisciplinary), Seizures, Seizures - genetics, Sodium, Sodium channels (voltage-gated)