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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.


Constance E. Clare

Amey H. Brassington

Wing Yee Kwong

Professor of Developmental Biology


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.


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), 263-287.

Journal Article Type Article
Acceptance Date Aug 29, 2018
Online Publication Date Nov 9, 2018
Publication Date Feb 15, 2019
Deposit Date Nov 19, 2018
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
Pages 263-287
Keywords Biotechnology; Animal Science and Zoology; Genetics; General Veterinary
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