Transposable elements: targets for early nutritional effects on epigenetic gene regulation.
Early nutrition affects adult metabolism in humans and other mammals, potentially via persistent alterations in DNA methylation. With viable yellow agouti (A(vy)) mice, which harbor a transposable element in the agouti gene, we tested the hypothesis that the metastable methylation status of specific transposable element insertion sites renders them epigenetically labile to early methyl donor nutrition. Our results show that dietary methyl supplementation of a/a dams with extra folic acid, vitamin B(12), choline, and betaine alter the phenotype of their A(vy)/a offspring via increased CpG methylation at the A(vy) locus and that the epigenetic metastability which confers this lability is due to the A(vy) transposable element. These findings suggest that dietary supplementation, long presumed to be purely beneficial, may have unintended deleterious influences on the establishment of epigenetic gene regulation in humans.
Waterland
Robert A
RA
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Jirtle
Randy L
RL
D000483:Alleles; D000818:Animals; D001622:Betaine / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D018899:CpG Islands; D019175:DNA Methylation; D004251:DNA Transposable Elements; D019587:Dietary Supplements; D005091:Exons; D005492:Folic Acid / Q000494:pharmacology; D005786:Gene Expression Regulation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009747:Nutritional Physiological Phenomena; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013447:Sulfites / Q000494:pharmacology; D014805:Vitamin B 12 / Q000494:pharmacology
D004251:DNA Transposable Elements; D013447:Sulfites; D001622:Betaine; D005492:Folic Acid; D002794:Choline; D014805:Vitamin B 12