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

Michelle L. Holland; Robert Lowe; Paul W. Caton; Carolina Gemma; Guillermo Carbajosa; Amy F. Danson; Asha M. Carpenter; Elena Loche; Susan E. Ozanne; Vardhman K. Rakyan

doi:10.1126/science.aaf7040

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

Michelle L. Holland, Robert Lowe, Paul W. Caton, Carolina Gemma, Guillermo Carbajosa, Amy F. Danson, Asha M. Carpenter, Elena Loche, Susan E. Ozanne, Vardhman K. Rakyan

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	495-498
Number of pages	4
Journal	Science
Volume	353
Issue number	6298
Early online date	7 Jul 2016
DOIs	https://doi.org/10.1126/science.aaf7040
Publication status	Published - 29 Jul 2016

Keywords

Animals
DNA Methylation
DNA, Ribosomal/genetics
Diet, High-Fat
Diet, Protein-Restricted
Epigenesis, Genetic
Female
Gene-Environment Interaction
Genetic Variation
Male
Maternal Nutritional Physiological Phenomena
Mice
Nutritional Status
Obesity/genetics
Pregnancy
Promoter Regions, Genetic
Weaning

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10.1126/science.aaf7040

Early life nutrition modulates the_HOLLAND_Accepted28June2016_GREEN AAMAccepted author manuscript, 807 KBLicence: Unspecified

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title = "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. ",

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author = "Holland, {Michelle L.} and Robert Lowe and Caton, {Paul W.} and Carolina Gemma and Guillermo Carbajosa and Danson, {Amy F.} and Carpenter, {Asha M.} and Elena Loche and Ozanne, {Susan E.} and Rakyan, {Vardhman K.}",

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AU - Holland, Michelle L.

AU - Lowe, Robert

AU - Caton, Paul W.

AU - Gemma, Carolina

AU - Carbajosa, Guillermo

AU - Danson, Amy F.

AU - Carpenter, Asha M.

AU - Loche, Elena

AU - Ozanne, Susan E.

AU - Rakyan, Vardhman K.

PY - 2016/7/29

Y1 - 2016/7/29

N2 - 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.

AB - 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.

KW - Animals

KW - DNA Methylation

KW - DNA, Ribosomal/genetics

KW - Diet, High-Fat

KW - Diet, Protein-Restricted

KW - Epigenesis, Genetic

KW - Female

KW - Gene-Environment Interaction

KW - Genetic Variation

KW - Male

KW - Maternal Nutritional Physiological Phenomena

KW - Mice

KW - Nutritional Status

KW - Obesity/genetics

KW - Pregnancy

KW - Promoter Regions, Genetic

KW - Weaning

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U2 - 10.1126/science.aaf7040

DO - 10.1126/science.aaf7040

M3 - Article

C2 - 27386920

SN - 0036-8075

VL - 353

SP - 495

EP - 498

JO - Science

JF - Science

IS - 6298

ER -

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

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Keywords

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