| First Author | Yoshida K | Year | 2020 |
| Journal | Mol Cell | Volume | 78 |
| Issue | 3 | Pages | 445-458.e6 |
| PubMed ID | 32197065 | Mgi Jnum | J:294263 |
| Mgi Id | MGI:6455260 | Doi | 10.1016/j.molcel.2020.02.028 |
| Citation | Yoshida K, et al. (2020) ATF7-Dependent Epigenetic Changes Are Required for the Intergenerational Effect of a Paternal Low-Protein Diet. Mol Cell 78(3):445-458.e6 |
| abstractText | 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 approximately 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. |
