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 and Peng Jin ()
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Xuekun Li: The Children’s Hospital and Institute of Translational Medicine, School of Medicine, Zhejiang University
Bing Yao: Emory University School of Medicine
Li Chen: Rollins School of Public Health, Emory University
Yunhee Kang: Emory University School of Medicine
Yujing Li: Emory University School of Medicine
Ying Cheng: Emory University School of Medicine
Liping Li: The Children’s Hospital and Institute of Translational Medicine, School of Medicine, Zhejiang University
Li Lin: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration, Ministry of Education of PRC, Jinan University
Zhiqin Wang: Emory University School of Medicine
Mengli Wang: Emory University School of Medicine
Feng Pan: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
Qing Dai: University of Chicago
Wei Zhang: College of Business, Iowa State University
Hao Wu: Rollins School of Public Health, Emory University
Qiang Shu: The Children’s Hospital and Institute of Translational Medicine, School of Medicine, Zhejiang University
Zhaohui Qin: Rollins School of Public Health, Emory University
Chuan He: University of Chicago
Mingjiang Xu: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
Peng Jin: The Children’s Hospital and Institute of Translational Medicine, School of Medicine, Zhejiang University

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms15903

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