Journal Articles

Choline, Other Methyl-Donors and Epigenetics

May 25, 2017

Steven H. Zeisel (2017). Choline, Other Methyl-Donors and Epigenetics. Nutrients 9(445).

Author Affiliations

UNC Nutrition Research Institute, Departments of Nutrition and Pediatrics, University of North Carolina at
Chapel Hill, 500 Laureate Drive, Kannapolis, NC 28081, USA;; Tel.: +1-704-250-5006


Choline dietary intake varies such that many people do not achieve adequate
intakes. Diet intake of choline can modulate methylation because, via betaine homocysteine
methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations
of S-adenosylhomocysteine and S-adenosylmethionine. Some of the epigenetic mechanisms that
modify gene expression without modifying the genetic code depend on the methylation of DNA or
of histones; and diet availability of choline and other methyl-group donors influences both of these
methylations. Examples of methyl-donor mediated epigenetic effects include the changes in coat
color and body weight in offspring when pregnant agouti mice are fed high choline, high methyl
diets; the changes in tail kinking in offspring when pregnant Axin(Fu) mice are fed high choline,
high methyl diets; the changes in Cdkn3 methylation and altered brain development that occurs in
offspring when pregnant rodents are fed low choline diets. When choline metabolism is disrupted
by deleting the gene Bhmt, DNA methylation is affected (especially in a region of chromosome 13),
expression of specific genes is suppressed, and liver cancers develop. Better understanding of how
nutrients such as choline and methyl-donors influence epigenetic programs has importance for our
understanding of not only developmental abnormalities but also for understanding the origins of
chronic diseases.

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