Ten-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis

Xuekun Li; Bing Yao; Li Chen; Yunhee Kang; Yujing Li; Ying Cheng; Liping Li; Li Lin; Zhiqin Wang; Mengli Wang; Feng Pan; Qing Dai; Wei Zhang; Hao Wu; Qiang Shu; Zhaohui Qin; Chuan He; Mingjiang Xu; Peng Jin

doi:10.1038/ncomms15903

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Ten-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis

Journal article

Open access

Peer reviewed

Ten-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis

Xuekun Li, Bing Yao, Li Chen, Yunhee Kang, Yujing Li, Ying Cheng, Liping Li, Li Lin, Zhiqin Wang, Mengli Wang, …

Nature communications, Vol.8(1), pp.15903-15903

2017-06-29

DOI: https://doi.org/10.1038/ncomms15903

PMCID: PMC5493768

PMID: 28660881

Abstract

5-Methylcytosine - analogs & derivatives

5-Methylcytosine - metabolism

Animals

Cell Proliferation

Cells, Cultured

DNA-Binding Proteins - genetics

DNA-Binding Proteins - metabolism

Forkhead Box Protein O3 - genetics

Forkhead Box Protein O3 - metabolism

Gene Expression Regulation

Male

Mice, Knockout

Neural Stem Cells - cytology

Neural Stem Cells - metabolism

Neurogenesis

Protein Binding

Proto-Oncogene Proteins - genetics

Proto-Oncogene Proteins - metabolism

Emerging evidence suggests that active DNA demethylation machinery plays important epigenetic roles in mammalian adult neurogenesis; however, the precise molecular mechanisms and critical functional players of DNA demethylation in this process remain largely unexplored. Ten-eleven translocation (Tet) proteins convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and its downstream derivatives. Here we show that 5hmC is elevated during the differentiation of adult neural stem cells (aNSCs), and Tet2 is primarily responsible for modulating 5hmC dynamics. Depletion of Tet2 leads to increased aNSC proliferation and reduced differentiation in vitro and in vivo. Genome-wide transcriptional analyses reveal important epigenetic roles of Tet2 in maintaining the transcriptome landscape related to neurogenesis. Mechanistically, transcription factor forkhead box O3 (Foxo3a) physically interacts with Tet2 and regulates the expression of genes related to aNSC proliferation. These data together establish an important role for the Tet2-Foxo3a axis in epigenetically regulating critical genes in aNSCs during adult neurogenesis.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.54 Molecular & Cell Biology - Genetics; 1.54.100 DNA Methylation
Web Of Science research areas: Cell Biology
ESI research areas: Molecular Biology & Genetics

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Title: Ten-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis
Creators: Xuekun Li - The Children's Hospital and Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China
Bing Yao - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Li Chen - Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, USA
Yunhee Kang - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Yujing Li - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Ying Cheng - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Liping Li - The Children's Hospital and Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China
Li Lin - Guangdong-Hongkong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration, Ministry of Education of PRC, Jinan University, Guangzhou 510632, PR China
Zhiqin Wang - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Mengli Wang - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Feng Pan - Sylvester Comprehensive Cancer Center, Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA
Qing Dai - Department of Chemistry, University of Chicago, Chicago, Ilinois 60637, USA
Wei Zhang - College of Business, Iowa State University, Ames, Iowa 50011, USA
Hao Wu - Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, USA
Qiang Shu - The Children's Hospital and Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China
Zhaohui Qin - Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, USA
Chuan He - Department of Chemistry, University of Chicago, Chicago, Ilinois 60637, USA
Mingjiang Xu - Sylvester Comprehensive Cancer Center, Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA
Peng Jin - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Publication Details: Nature communications, Vol.8(1), pp.15903-15903
Grant note: R01 NS079625 / NINDS NIH HHS R01 NS051630 / NINDS NIH HHS R01 MH102690 / NIMH NIH HHS P01 NS097206 / NINDS NIH HHS RM1 HG008935 / NHGRI NIH HHS
Language: English
Resource Type: Journal article
PMID: 28660881
PMCID: PMC5493768
Record Identifier: 991031614246002976