Loss of TET Activity in the Postnatal Mouse Brain Perturbs Synaptic Gene Expression and Impairs Cognitive Function.
10.1007/s12264-024-01302-2
- Author:
Ji-Wei LIU
1
;
Ze-Qiang ZHANG
2
;
Zhi-Chuan ZHU
3
;
Kui LI
3
;
Qiwu XU
3
;
Jing ZHANG
3
;
Xue-Wen CHENG
3
;
Han LI
4
;
Ying SUN
1
;
Ji-Jun WANG
4
;
Lu-Lu HU
5
;
Zhi-Qi XIONG
6
;
Yongchuan ZHU
7
Author Information
1. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
2. University of Chinese Academy of Sciences, Beijing, 100049, China.
3. Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 20031, China.
4. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
5. Fudan University Institutes of Biomedical Sciences, Shanghai Cancer Center, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Shanghai Medical College of Fudan University, Shanghai, 200032, China.
6. University of Chinese Academy of Sciences, Beijing, 100049, China. xiongzhiqi@ion.ac.cn.
7. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. yczhu@smhc.org.cn.
- Publication Type:Journal Article
- Keywords:
5hmC;
DNA demethylation;
Epigenetics;
Learning and memory;
Synapse;
TET
- MeSH:
Animals;
Brain/growth & development*;
5-Methylcytosine/metabolism*;
Mice;
Synapses/genetics*;
Proto-Oncogene Proteins/metabolism*;
DNA-Binding Proteins/metabolism*;
Dioxygenases/metabolism*;
Cognition/physiology*;
Gene Expression;
Mixed Function Oxygenases/metabolism*;
Epigenesis, Genetic;
Mice, Knockout;
Mice, Inbred C57BL
- From:
Neuroscience Bulletin
2024;40(11):1699-1712
- CountryChina
- Language:English
-
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.
