Paternal Age Affects Offspring Via an Epigenetic Mechanism Involving REST/NRSF

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2021 Jan 5

PMID 33399271

Citations 30

Authors

Kaichi Yoshizaki

Ryuichi Kimura

Hisato Kobayashi

Shinya Oki

Takako Kikkawa

Lingling Mai

Kohei Koike

Kentaro Mochizuki

Hitoshi Inada

Yasuhisa Matsui

Tomohiro Kono

Noriko Osumi

Affiliations

Soon will be listed here.

Abstract

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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