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Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice.

ABSTRACT: A suboptimal early-life environment, due to poor nutrition or stress during pregnancy, can influence lifelong phenotypes in the progeny. Epigenetic factors are thought to be key mediators of these effects. We show that protein restriction in mice from conception until weaning induces a linear correlation between growth restriction and DNA methylation at ribosomal DNA (rDNA). This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic variant within the promoter. Related effects are also found in models of maternal high-fat or obesogenic diets. Our work identifies environmentally induced epigenetic dynamics that are dependent on underlying genetic variation and establishes rDNA as a genomic target of nutritional insults.

SUBMITTER: Holland ML

PROVIDER: S-EPMC5734613 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice.

Holland Michelle L ML Lowe Robert R Caton Paul W PW Gemma Carolina C Carbajosa Guillermo G Danson Amy F AF Carpenter Asha A M AA Loche Elena E Ozanne Susan E SE Rakyan Vardhman K VK

Science (New York, N.Y.) 20160707 6298

A suboptimal early-life environment, due to poor nutrition or stress during pregnancy, can influence lifelong phenotypes in the progeny. Epigenetic factors are thought to be key mediators of these effects. We show that protein restriction in mice from conception until weaning induces a linear correlation between growth restriction and DNA methylation at ribosomal DNA (rDNA). This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic varian ...[more]

PMID: 27386920

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