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

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... Full description

Journal Title: Nature Communications 2017, Vol.8
Main Author: Xuekun Li
Other Authors: 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
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ID: ISSN: 2041-1723 ; E-ISSN: 2041-1723 ; DOI: 10.1038/ncomms15903
Link: http://dx.doi.org/10.1038/ncomms15903
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recordid: nature_a10.1038/ncomms15903
title: Ten-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis
format: Article
creator:
  • 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
subjects:
  • Biology
ispartof: Nature Communications, 2017, Vol.8
description: 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.
language:
source:
identifier: ISSN: 2041-1723 ; E-ISSN: 2041-1723 ; DOI: 10.1038/ncomms15903
fulltext: fulltext
issn:
  • 2041-1723
  • 20411723
url: Link


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titleTen-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis
creatorXuekun 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
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descriptionEmerging 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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authorXuekun 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
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