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Dynamics of ten-eleven translocation hydroxylase family proteins and 5-hydroxymethylcytosine in oligodendrocyte differentiation

Authors

  • Xianghui Zhao,

    Corresponding author
    1. Institute of Neuroscience, Fourth Military Medical University, Xi'an, China
    • Address correspondence to Dr. Xianghui Zhao, Institute of Neuroscience, Fourth Military Medical University, 169 Changle Xi Road, Xi'an 710032, China. E-mail: xianghuizhao@fmmu.edu.cn (or) Dr. Weilin Jin, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Minhang, Shanghai 200240, China. E-mail: weilinjin@yahoo.com or weilinjin@sjtu.edu.cn

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    • These authors contribute equally to this article.

  • Jinxiang Dai,

    1. Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Research Institute of Micro/Nano Science and Technology, Bio-X Center, Shanghai Jiao Tong University, Shanghai, China
    2. Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado
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    • These authors contribute equally to this article.

  • Yue Ma,

    1. Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Research Institute of Micro/Nano Science and Technology, Bio-X Center, Shanghai Jiao Tong University, Shanghai, China
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  • Yajing Mi,

    1. School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
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  • Daxiang Cui,

    1. Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Research Institute of Micro/Nano Science and Technology, Bio-X Center, Shanghai Jiao Tong University, Shanghai, China
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  • Gong Ju,

    1. Institute of Neuroscience, Fourth Military Medical University, Xi'an, China
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  • Wendy B. Macklin,

    1. Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado
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  • Weilin Jin

    1. Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Research Institute of Micro/Nano Science and Technology, Bio-X Center, Shanghai Jiao Tong University, Shanghai, China
    2. School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
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Abstract

The ten-eleven translocation (TET) family of methylcytosine dioxygenases catalyze oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and promote DNA demethylation. Despite the abundance of 5hmC and TET proteins in the brain, little is known about their role in oligodendrocytes (OLs). Here, we analyzed TET expression during OL development in vivo and in vitro, and found that three TET family members possess unique subcellular and temporal expression patterns. Furthermore, the level of 5hmC exhibits dynamic changes during OL maturation, which implies that 5hmC modification may play a role in the expression of critical genes necessary for OL maturation. siRNA-mediated silencing of the TET family proteins in OLs demonstrated that each of the TET proteins is required for OL differentiation. However, based on their unique domain structures, we speculate that the three TET members may function by different mechanisms. In summary, we have established the temporal expression of TET proteins and the dynamic level of 5hmC during OL development and demonstrate that all three TET members are necessary for OL differentiation. GLIA 2014;62:914–926

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