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Paternal age affects offspring via an epigenetic mechanism involving REST/NRSF
Author(s) -
Yoshizaki Kaichi,
Kimura Ryuichi,
Kobayashi Hisato,
Oki Shinya,
Kikkawa Takako,
Mai Lingling,
Koike Kohei,
Mochizuki Kentaro,
Inada Hitoshi,
Matsui Yasuhisa,
Kono Tomohiro,
Osumi Noriko
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202051524
Subject(s) - library science , research center , medical school , medicine , medical education , pathology , computer science
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.