首页|Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis,Synaptic Plasticity,and Cognitive Behavior in Mice

Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis,Synaptic Plasticity,and Cognitive Behavior in Mice

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The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit(EZH2)-medi-ated 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 den-dritic spine density.Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal mor-phogenesis.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 neg-ative 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.

Neural developmentDendritic branchingDendritic spineCognitive functionEpigeneticsHistone methylationEZH2

Mei Zhang、Yong Zhang、Qian Xu、Joshua Crawford、Cheng Qian、Guo-Hua Wang、Jiang Qian、Xin-Zhong Dong、Mikhail V.Pletnikov、Chang-Mei Liu、Feng-Quan Zhou

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Department of Orthopaedic Surgery,Johns Hopkins University School of Medicine,Baltimore 21205,USA

School of Life Sciences,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230026,China

The Solomon H.Snyder Department of Neuroscience,Johns Hopkins University School of Medicine,Baltimore 21205,USA

Department of Psychiatry and Behavioral Sciences,Johns Hopkins University School of Medicine,Baltimore 21205,USA

Department of Ophthalmology,Johns Hopkins University School of Medicine,Baltimore 21205,USA

State Key Laboratory of Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100190,China

Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016,China

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NIHNIHNIHNIHCraig H.Neilsen FoundationBrightFocus Foundation

R01NS064288R01NS085176R01GM111514R01EY027347259450G2017037

2023

10.1007/s12264-023-01074-1

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子：0.741
ISSN：1673-7067
年,卷(期)：2023.39(10)
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