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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Article number15903
JournalNature Communications
Volume8
DOIs
StatePublished - Jun 29 2017

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Adult Stem Cells
Neural Stem Cells
Neurogenesis
Stem cells
boxes
stem cells
Genes
Cell proliferation
Epigenomics
Cell Proliferation
5-Methylcytosine
Forkhead Transcription Factors
genes
DNA
Protein Transport
deoxyribonucleic acid
Transcriptome
Machinery
genome
machinery

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Ten-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis. / Li, Xuekun; Yao, Bing; Chen, Li; Kang, Yunhee; Li, Yujing; Cheng, Ying; Li, Liping; Lin, Li; Wang, Zhiqin; Wang, Mengli; Pan, Feng; Dai, Qing; Zhang, Wei; Wu, Hao; Shu, Qiang; Qin, Zhaohui; He, Chuan; Xu, Mingjiang; Jin, Peng.

In: Nature Communications, Vol. 8, 15903, 29.06.2017.

Research output: Contribution to journalArticle

Li, X, Yao, B, Chen, L, Kang, Y, Li, Y, Cheng, Y, Li, L, Lin, L, Wang, Z, Wang, M, Pan, F, Dai, Q, Zhang, W, Wu, H, Shu, Q, Qin, Z, He, C, Xu, M & Jin, P 2017, 'Ten-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis', Nature Communications, vol. 8, 15903. https://doi.org/10.1038/ncomms15903
Li, Xuekun ; Yao, Bing ; Chen, Li ; Kang, Yunhee ; Li, Yujing ; Cheng, Ying ; Li, Liping ; Lin, Li ; Wang, Zhiqin ; Wang, Mengli ; Pan, Feng ; Dai, Qing ; Zhang, Wei ; Wu, Hao ; Shu, Qiang ; Qin, Zhaohui ; He, Chuan ; Xu, Mingjiang ; Jin, Peng. / Ten-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis. In: Nature Communications. 2017 ; Vol. 8.
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AU - Jin, Peng

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