Departments of Pediatrics and Molecular and Human Genetics; Baylor College of Medicine, Children's Nutrition Research Center
Human epidemiologic data indicate that nutrition during prenatal and early postnatal development can affect susceptibility to various chronic diseases in adulthood, including cardiovascular disease, type-2 diabetes, obesity, and cancer. Controlled studies in animal models corroborate that nutritional exposures during critical periods of development can wield lasting influences on gene expression and metabolism, but our understanding of the fundamental biologic mechanisms underlying such phenomena remains rudimentary (1).
Nutritional influences on the developmental establishment of epigenetic gene regulatory mechanisms could link early nutrition to adult chronic disease susceptibility (2). Epigenetics is the study of mitotically and/or meiotically heritable alterations in gene expression that are not associated with changes in DNA sequence. Just as genetic variation contributes to individual susceptibility to chronic disease, it is increasingly evident that so too does individual epigenetic variation. We know very little, however, about the factors that contribute to interindividual variation in epigenotype. It is critically important to determine if nutrition and other environmental influences during development affect the establishment of human epigenotype.
Epigenetic mechanisms and fundamental concepts of developmental epigenetics will be discussed. Attention will be focused on the epigenetic mechanism of CpG methylation, and the critical role of nutrition in providing the methyl donors necessary for this covalent modification of DNA. Recent data demonstrating early nutritional influences on the development of locus-specific CpG methylation and associated phenotypes in mouse models will be reviewed. Key research questions will be proposed to guide future studies in nutritional epigenetics. (Supported by NIH grant DK063781, USDA CRIS #6250-51000-049 and research grant #5-FY05-47 from the March of Dimes.)
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Waterland RA, and Jirtle RL. Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition 20:63-68, 2004.