Loss of TET Activity in the Postnatal Mouse Brain Perturbs Synaptic Gene Expression and Impairs Cognitive Function.

IF 5.9 2区 医学 Q1 NEUROSCIENCES
Ji-Wei Liu, Ze-Qiang Zhang, Zhi-Chuan Zhu, Kui Li, Qiwu Xu, Jing Zhang, Xue-Wen Cheng, Han Li, Ying Sun, Ji-Jun Wang, Lu-Lu Hu, Zhi-Qi Xiong, Yongchuan Zhu
{"title":"Loss of TET Activity in the Postnatal Mouse Brain Perturbs Synaptic Gene Expression and Impairs Cognitive Function.","authors":"Ji-Wei Liu, Ze-Qiang Zhang, Zhi-Chuan Zhu, Kui Li, Qiwu Xu, Jing Zhang, Xue-Wen Cheng, Han Li, Ying Sun, Ji-Jun Wang, Lu-Lu Hu, Zhi-Qi Xiong, Yongchuan Zhu","doi":"10.1007/s12264-024-01302-2","DOIUrl":null,"url":null,"abstract":"<p><p>Conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins leads to the accumulation of 5hmC in the central nervous system; however, the role of 5hmC in the postnatal brain and how its levels and target genes are regulated by TETs remain elusive. We have generated mice that lack all three Tet genes specifically in postnatal excitatory neurons. These mice exhibit significantly reduced 5hmC levels, altered dendritic spine morphology within brain regions crucial for cognition, and substantially impaired spatial and associative memories. Transcriptome profiling combined with epigenetic mapping reveals that a subset of genes, which display changes in both 5hmC/5mC levels and expression patterns, are involved in synapse-related functions. Our findings provide insight into the role of postnatally accumulated 5hmC in the mouse brain and underscore the impact of 5hmC modification on the expression of genes essential for synapse development and function.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.9000,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroscience bulletin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12264-024-01302-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

Conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins leads to the accumulation of 5hmC in the central nervous system; however, the role of 5hmC in the postnatal brain and how its levels and target genes are regulated by TETs remain elusive. We have generated mice that lack all three Tet genes specifically in postnatal excitatory neurons. These mice exhibit significantly reduced 5hmC levels, altered dendritic spine morphology within brain regions crucial for cognition, and substantially impaired spatial and associative memories. Transcriptome profiling combined with epigenetic mapping reveals that a subset of genes, which display changes in both 5hmC/5mC levels and expression patterns, are involved in synapse-related functions. Our findings provide insight into the role of postnatally accumulated 5hmC in the mouse brain and underscore the impact of 5hmC modification on the expression of genes essential for synapse development and function.

出生后小鼠大脑中 TET 活性的丧失会干扰突触基因表达并损害认知功能
十-十一转位(TET)家族蛋白将 5-甲基胞嘧啶(5mC)转化为 5-羟甲基胞嘧啶(5hmC)会导致 5hmC 在中枢神经系统中的积累;然而,5hmC 在出生后大脑中的作用以及其水平和靶基因如何受 TETs 的调控仍是未知数。我们培育出了在出生后兴奋性神经元中特异性缺乏全部三种 TET 基因的小鼠。这些小鼠的 5hmC 水平明显降低,对认知至关重要的大脑区域内的树突棘形态发生改变,空间记忆和联想记忆受到严重损害。转录组图谱分析与表观遗传图谱相结合发现,5hmC/5mC水平和表达模式均发生变化的基因子集参与了突触相关功能。我们的研究结果让人们深入了解了出生后积累的 5hmC 在小鼠大脑中的作用,并强调了 5hmC 修饰对突触发育和功能所必需的基因表达的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Neuroscience bulletin
Neuroscience bulletin NEUROSCIENCES-
CiteScore
7.20
自引率
16.10%
发文量
163
审稿时长
6-12 weeks
期刊介绍: Neuroscience Bulletin (NB), the official journal of the Chinese Neuroscience Society, is published monthly by Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Springer. NB aims to publish research advances in the field of neuroscience and promote exchange of scientific ideas within the community. The journal publishes original papers on various topics in neuroscience and focuses on potential disease implications on the nervous system. NB welcomes research contributions on molecular, cellular, or developmental neuroscience using multidisciplinary approaches and functional strategies. We feature full-length original articles, reviews, methods, letters to the editor, insights, and research highlights. As the official journal of the Chinese Neuroscience Society, which currently has more than 12,000 members in China, NB is devoted to facilitating communications between Chinese neuroscientists and their international colleagues. The journal is recognized as the most influential publication in neuroscience research in China.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信