Paternal age affects offspring via an epigenetic mechanism involving REST/NRSF | Zendy

Yoshizaki Kaichi | Zendy; Kimura Ryuichi | Zendy; Kobayashi Hisato | Zendy; Oki Shinya | Zendy; Kikkawa Takako | Zendy; Mai Lingling | Zendy; Koike Kohei | Zendy; Mochizuki Kentaro | Zendy; Inada Hitoshi | Zendy; Matsui Yasuhisa | Zendy; Kono Tomohiro | Zendy; Osumi Noriko | Zendy

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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) - offspring , epigenetics , rest (music) , mechanism (biology) , epigenesis , biology , genetics , medicine , dna methylation , gene , pregnancy , gene expression , philosophy , epistemology

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.

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