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DNA DYNAMICS AND CHROMOSOME STRUCTURE

Transposable Elements: Targets for Early Nutritional Effects on Epigenetic Gene Regulation

Robert A. Waterland, Randy L. Jirtle
Robert A. Waterland
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710
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Randy L. Jirtle
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710
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  • For correspondence: jirtle@radonc.duke.edu
DOI: 10.1128/MCB.23.15.5293-5300.2003
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ABSTRACT

Early nutrition affects adult metabolism in humans and other mammals, potentially via persistent alterations in DNA methylation. With viable yellow agouti (Avy ) 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 B12, choline, and betaine alter the phenotype of their Avy/a offspring via increased CpG methylation at the Avy locus and that the epigenetic metastability which confers this lability is due to the Avy 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.

  • Copyright © 2003 American Society for Microbiology
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Transposable Elements: Targets for Early Nutritional Effects on Epigenetic Gene Regulation
Robert A. Waterland, Randy L. Jirtle
Molecular and Cellular Biology Aug 2003, 23 (15) 5293-5300; DOI: 10.1128/MCB.23.15.5293-5300.2003

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Transposable Elements: Targets for Early Nutritional Effects on Epigenetic Gene Regulation
Robert A. Waterland, Randy L. Jirtle
Molecular and Cellular Biology Aug 2003, 23 (15) 5293-5300; DOI: 10.1128/MCB.23.15.5293-5300.2003
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KEYWORDS

DNA methylation
DNA Transposable Elements
Gene Expression Regulation
Nutritional Physiological Phenomena

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