PT  - JOURNAL ARTICLE
AU  - Mei Zhang
AU  - Yong Zhang
AU  - Qian Xu
AU  - Joshua Crawford
AU  - Cheng Qian
AU  - Guo-Hua Wang
AU  - Eastman Lewis
AU  - Philip Hall
AU  - Gül Dolen
AU  - Richard L. Huganir
AU  - Jiang Qian
AU  - Xin-Zhong Dong
AU  - Mikhail V. Pletnikov
AU  - Chang-Mei Liu
AU  - Feng-Quan Zhou
TI  - Neuronal histone methyltransferase EZH2 regulates neuronal morphogenesis, synaptic plasticity, and cognitive behavior of mice
AID  - 10.1101/582908
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 582908
4099  - http://biorxiv.org/content/early/2019/03/20/582908.short
4100  - http://biorxiv.org/content/early/2019/03/20/582908.full
AB  - Recent studies showed that in the nervous system histone methyltransferase EZH2-mediated trimethylation of histone H3 lysine 27 (H3K27me3) acts to regulate neural stem cell proliferation and fate specificity through silencing different gene sets. Here we explored the function of EZH2 in early post-mitotic excitatory neurons by generating a neuronal specific Ezh2 conditional knockout mouse line. The results showed that lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and significantly increased dendritic spine density. RNA-sequencing (RNA-seq) experiments comparing control and Ezh2 knockout neurons revealed that neuronal EZH2 regulated genes related to neuronal morphogenesis. In particular, Pak3 was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of dominant negative PAK3 reversed Ezh2 knockout-induced higher dendritic spine density. Lastly, lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 played important roles in controlling multiple steps of neuronal morphogenesis during development, which had long-lasting effects on cognitive function in adult mice.