| First Author | Yoshizaki K | Year | 2021 |
| Journal | EMBO Rep | Volume | 22 |
| Issue | 2 | Pages | e51524 |
| PubMed ID | 33399271 | Mgi Jnum | J:316865 |
| Mgi Id | MGI:6712134 | Doi | 10.15252/embr.202051524 |
| Citation | Yoshizaki K, et al. (2021) Paternal age affects offspring via an epigenetic mechanism involving REST/NRSF. EMBO Rep 22(2):e51524 |
| abstractText | Advanced paternal age can have deleterious effects on various traits in the next generation. Here, we establish a paternal-aging model in mice to understand the molecular mechanisms of transgenerational epigenetics. Whole-genome target DNA methylome analyses of sperm from aged mice reveal more hypo-methylated genomic regions enriched in REST/NRSF binding motifs. Gene set enrichment analyses also reveal the upregulation of REST/NRSF target genes in the forebrain of embryos from aged fathers. Offspring derived from young mice administrated with a DNA de-methylation drug phenocopy the abnormal vocal communication of pups derived from aged fathers. In conclusion, hypo-methylation of sperm DNA can be a key molecular feature modulating neurodevelopmental programs in offspring by causing fluctuations in the expression of REST/NRSF target genes. |
