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One-Carbon Metabolism: Linking Nutritional Biochemistry to Epigenetic Programming of Long-Term Development

Clare, Constance E.; Brassington, Amey H.; Kwong, Wing Yee; Sinclair, Kevin D.

Authors

Constance E. Clare

Amey H. Brassington

Wing Yee Kwong

KEVIN SINCLAIR kevin.sinclair@nottingham.ac.uk
Professor of Developmental Biology



Abstract

One-carbon (1C) metabolism comprises a series of interlinking metabolic pathways that include the methionine and folate cycles that are central to cellular function, providing 1C units (methyl groups) for the synthesis of DNA, polyamines, amino acids, creatine, and phospholipids. Sadenosylmethionine is a potent aminopropyl and methyl donor within these cycles and serves as the principal substrate for methylation of DNA, associated proteins, and RNA. We propose that 1C metabolism functions as a key biochemical conduit between parental environment and epigenetic regulation of early development and that interindividual and ethnic variability in epigenetic-gene regulation arises because of genetic variants within 1C genes, associated epigenetic regulators, and differentially methylated target DNA sequences. We present evidence to support these propositions, drawing upon studies undertaken in humans and animals. We conclude that future studies should assess the epigenetic effects of cumulative (multigenerational) dietary imbalances contemporaneously in both parents, as this better represents the human experience.

Journal Article Type Article
Publication Date Feb 15, 2019
Journal Annual Review of Animal Biosciences
Print ISSN 2165-8102
Electronic ISSN 2165-8110
Publisher Annual Reviews
Peer Reviewed Peer Reviewed
Volume 7
Issue 1
APA6 Citation Clare, C. E., Brassington, A. H., Kwong, W. Y., & Sinclair, K. D. (2019). One-Carbon Metabolism: Linking Nutritional Biochemistry to Epigenetic Programming of Long-Term Development. Annual Review of Animal Biosciences, 7(1), doi:10.1146/annurev-animal-020518-115206
DOI https://doi.org/10.1146/annurev-animal-020518-115206
Keywords Biotechnology; Animal Science and Zoology; Genetics; General Veterinary
Publisher URL https://www.annualreviews.org/doi/10.1146/annurev-animal-020518-115206
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