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Research Article
Dnd1-mediated epigenetic control of teratoma formation in mouse
Wei Gu, Kentaro Mochizuki, Kei Otsuka, Ryohei Hamada, Asuka Takehara, Yasuhisa Matsui
Biology Open 2018 7: bio032318 doi: 10.1242/bio.032318 Published 29 January 2018
Wei Gu
1Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
2Laboratory of Germ Cell Development, Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan
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Kentaro Mochizuki
1Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
2Laboratory of Germ Cell Development, Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan
3The Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo 100-0004, Japan
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Kei Otsuka
1Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
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Ryohei Hamada
1Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
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Asuka Takehara
1Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
3The Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo 100-0004, Japan
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Yasuhisa Matsui
1Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
2Laboratory of Germ Cell Development, Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan
3The Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo 100-0004, Japan
4Center for Regulatory Epigenome and Diseases, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
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  • ORCID record for Yasuhisa Matsui
  • For correspondence: yasuhisa.matsui.d3@tohoku.ac.jp
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ABSTRACT

Spontaneous testicular teratoma develops from primordial germ cells (PGCs) in embryos; however, the molecular mechanisms underlying teratoma formation are not fully understood. Mutation of the dead-end 1 (Dnd1) gene, which encodes an RNA-binding protein, drastically enhances teratoma formation in the 129/Sv mouse strain. To elucidate the mechanism of Dnd1 mutation-induced teratoma formation, we focused on histone H3 lysine 27 (H3K27) trimethylation (me3), and found that the levels of H3K27me3 and its responsible methyltransferase, enhancer of zeste homolog 2 (Ezh2), were decreased in the teratoma-forming cells of Dnd1 mutant embryos. We also showed that Dnd1 suppressed miR-26a-mediated inhibition of Ezh2 expression, and that Dnd1 deficiency resulted in decreased H3K27me3 of a cell-cycle regulator gene, Ccnd1. In addition, Ezh2 expression or Ccnd1 deficiency repressed the reprogramming of PGCs into pluripotent stem cells, which mimicked the conversion of embryonic germ cells into teratoma-forming cells. These results revealed an epigenetic molecular linkage between Dnd1 and the suppression of testicular teratoma formation.

Footnotes

  • Competing interests

    The authors declare no competing or financial interests.

  • Author contributions

    Conceptualization: W.G., K.M., Y.M.; Methodology: K.M., K.O.; Investigation: W.G., R.H., A.T.; Writing – original draft: W.G., Y.M.; Writing – review & editing: Y.M.; Supervision: Y.M.; Project administration: Y.M.; Funding acquisition: Y.M.

  • Funding

    This work was partly supported by a Grant-in-Aid for Scientific Research (KAKENHI) (25114003) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by AMED-CREST from the Japan Agency for Medical Research and Development (JP17gm0510017h).

  • Supplementary information

    Supplementary information available online at http://bio.biologists.org/lookup/doi/10.1242/bio.032318.supplemental

  • Received December 26, 2017.
  • Accepted January 2, 2018.
  • © 2018. Published by The Company of Biologists Ltd

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Keywords

  • Primordial germ cell
  • Teratoma
  • Histone methylation
  • Dnd1

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Research Article
Dnd1-mediated epigenetic control of teratoma formation in mouse
Wei Gu, Kentaro Mochizuki, Kei Otsuka, Ryohei Hamada, Asuka Takehara, Yasuhisa Matsui
Biology Open 2018 7: bio032318 doi: 10.1242/bio.032318 Published 29 January 2018
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Research Article
Dnd1-mediated epigenetic control of teratoma formation in mouse
Wei Gu, Kentaro Mochizuki, Kei Otsuka, Ryohei Hamada, Asuka Takehara, Yasuhisa Matsui
Biology Open 2018 7: bio032318 doi: 10.1242/bio.032318 Published 29 January 2018

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