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[sup 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[sub 12], choline, and betaine alter the phenotype of their A[sup vy]/a offspring via increased CpG methylation at the A[sup vy] locus and that the epigenetic metastability which confers this lability is due to the A[sup 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. [ABSTRACT FROM AUTHOR]