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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