Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis, Synaptic Plasticity, and Cognitive Behavior in Mice.
10.1007/s12264-023-01074-1
- Author:
Mei ZHANG
1
;
Yong ZHANG
2
;
Qian XU
2
;
Joshua CRAWFORD
3
;
Cheng QIAN
1
;
Guo-Hua WANG
4
;
Jiang QIAN
4
;
Xin-Zhong DONG
2
;
Mikhail V PLETNIKOV
3
;
Chang-Mei LIU
5
;
Feng-Quan ZHOU
6
Author Information
1. Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, 21205, USA.
2. The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, 21205, USA.
3. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, 21205, USA.
4. Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, 21205, USA.
5. Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, 21205, USA. liuchm@ioz.ac.cn.
6. Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, 21205, USA. fzhou4@zju.edu.cn.
- Publication Type:Journal Article
- Keywords:
Cognitive function;
Dendritic branching;
Dendritic spine;
EZH2;
Epigenetics;
Histone methylation;
Neural development
- MeSH:
Animals;
Mice;
Enhancer of Zeste Homolog 2 Protein/metabolism*;
Histone Methyltransferases/metabolism*;
Histones/genetics*;
Morphogenesis;
Neuronal Plasticity;
Neurons/metabolism*
- From:
Neuroscience Bulletin
2023;39(10):1512-1532
- CountryChina
- Language:English
-
Abstract:
The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)-mediated trimethylation of histone H3 lysine 27 (H3K27me3) regulates neural stem cell proliferation and fate specificity through silencing different gene sets in the central nervous system. Here, we explored the function of EZH2 in early post-mitotic neurons by generating a neuron-specific Ezh2 conditional knockout mouse line. The results showed that a lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and increased dendritic spine density. Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal morphogenesis. In particular, the gene encoding p21-activated kinase 3 (Pak3) was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of the dominant negative Pak3 reversed Ezh2 knockout-induced higher dendritic spine density. Finally, the lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 acts to control multiple steps of neuronal morphogenesis during development, and has long-lasting effects on cognitive function in adult mice.
