Dnd1-mediated epigenetic control of teratoma formation in mouse

Wei Gu, Kentaro Mochizuki, Kei Otsuka, Ryohei Hamada, Asuka Takehara, Yasuhisa Matsui

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Spontaneous testicular teratoma develops from primordial germ cells (PGCs) in embryos; however, the molecular mechanisms underlying teratomaformation 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 expressionorCcnd1deficiency 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.

Original languageEnglish
Article numberbio032318
JournalBiology Open
Volume7
Issue number1
DOIs
Publication statusPublished - 2018

Keywords

  • Dnd1
  • Histone methylation
  • Primordial germ cell
  • Teratoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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