Molecular and Cellular Biology, August 2003, p. 5293-5300, Vol. 23, No. 15
0270-7306/03/$08.00+0 DOI: 10.1128/MCB.23.15.5293-5300.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Transposable Elements: Targets for Early Nutritional Effects on Epigenetic Gene Regulation
Robert A. Waterland and Randy L. Jirtle*
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710
Received 7 January 2003/
Returned for modification 14 April 2003/
Accepted 8 May 2003
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.
* Corresponding author. Mailing address: Duke University Medical Center, Department of Radiation Oncology, Box 3433, Durham, NC 27710. Phone: (919) 684-6203. Fax: (919) 684-5584. E-mail: jirtle{at}radonc.duke.edu.
Molecular and Cellular Biology, August 2003, p. 5293-5300, Vol. 23, No. 15
0022-538X/03/$08.00+0 DOI: 10.1128/MCB.23.15.5293-5300.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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