Genome-wide DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) residing in mouse pluripotent stem cells

Authors

  • Shinya Sato,

    1. Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, the University of Tokyo, Tokyo 113-8657, Japan
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    • These authors contributed equally to this work.

  • Shintaro Yagi,

    1. Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, the University of Tokyo, Tokyo 113-8657, Japan
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    • These authors contributed equally to this work.

  • Yoshikazu Arai,

    1. Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, the University of Tokyo, Tokyo 113-8657, Japan
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  • Keiji Hirabayashi,

    1. Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, the University of Tokyo, Tokyo 113-8657, Japan
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  • Naoko Hattori,

    1. Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, the University of Tokyo, Tokyo 113-8657, Japan
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  • Misa Iwatani,

    1. Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, the University of Tokyo, Tokyo 113-8657, Japan
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  • Keisuke Okita,

    1. Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507, Japan
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  • Jun Ohgane,

    1. Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, the University of Tokyo, Tokyo 113-8657, Japan
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  • Satoshi Tanaka,

    1. Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, the University of Tokyo, Tokyo 113-8657, Japan
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  • Teruhiko Wakayama,

    1. Laboratory for Genomic Programming, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
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  • Shinya Yamanaka,

    1. Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507, Japan
    2. Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
    3. Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94518, USA
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  • Kunio Shiota

    Corresponding author
    1. Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, the University of Tokyo, Tokyo 113-8657, Japan
    2. National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8561, Japan
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Communicated by: Shinichi AizawaCorrespondence: ashiota@mail.ecc.u-tokyo.ac.jp

Abstract

DNA methylation profile, consisting of tissue-dependent and differentially methylated regions (T-DMRs), has elucidated tissue-specific gene function in mouse tissues. Here, we identified and profiled thousands of T-DMRs in embryonic stem cells (ESCs), embryonic germ cells (EGCs) and induced pluripotent stem cells (iPSCs). T-DMRs of ESCs compared with somatic tissues well illustrated gene function of ESCs, by hypomethylation at genes associated with CpG islands and nuclear events including transcriptional regulation network of ESCs, and by hypermethylation at genes for tissue-specific function. These T-DMRs in EGCs and iPSCs showed DNA methylation similar to ESCs. iPSCs, however, showed hypomethylation at a considerable number of T-DMRs that were hypermethylated in ESCs, suggesting existence of traceable progenitor epigenetic information. Thus, DNA methylation profile of T-DMRs contributes to the mechanism of pluripotency, and can be a feasible solution for identification and evaluation of the pluripotent cells.

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