ATF7-Dependent Epigenetic Changes Are Required for the Intergenerational Effect of a Paternal Low-Protein Diet

Keisuke Yoshida, Toshio Maekawa, Nhung Hong Ly, Shin ichiro Fujita, Masafumi Muratani, Minami Ando, Yuki Katou, Hiromitsu Araki, Fumihito Miura, Katsuhiko Shirahige, Mariko Okada, Takashi Ito, Bruno Chatton, Shunsuke Ishii

研究成果: Contribution to journalArticle査読

10 被引用数 (Scopus)

抄録

Paternal dietary conditions may contribute to metabolic disorders in offspring. We have analyzed the role of the stress-dependent epigenetic regulator cyclic AMP-dependent transcription factor 7 (ATF7) in paternal low-protein diet (pLPD)-induced gene expression changes in mouse liver. Atf7+/– mutations cause an offspring phenotype similar to that caused by pLPD, and the effect of pLPD almost vanished when paternal Atf7+/– mice were used. ATF7 binds to the promoter regions of ∼2,300 genes, including cholesterol biosynthesis-related and tRNA genes in testicular germ cells (TGCs). LPD induces ATF7 phosphorylation by p38 via reactive oxygen species (ROS) in TGCs. This leads to the release of ATF7 and a decrease in histone H3K9 dimethylation (H3K9me2) on its target genes. These epigenetic changes are maintained and induce expression of some tRNA fragments in spermatozoa. These results indicate that LPD-induced and ATF7-dependent epigenetic changes in TGCs play an important role in paternal diet-induced metabolic reprograming in offspring.

本文言語英語
ページ(範囲)445-458.e6
ジャーナルMolecular Cell
78
3
DOI
出版ステータス出版済み - 5 7 2020

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学

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