Title:Choline Nutrition Programs Brain Development Via DNA and Histone Methylation
VOLUME: 12 ISSUE: 2
Author(s):Jan Krzysztof Blusztajn and Tiffany J. Mellott
Affiliation:Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 72 East Concord Street, L808, Boston, MA 02118, USA.
Keywords:Brain, choline, DNA, histone, memory, methylation, nutrition, pregnancy
Abstract:Choline is an essential nutrient for humans. Metabolically choline is used for the synthesis of membrane
phospholipids (e.g. phosphatidylcholine), as a precursor of the neurotransmitter acetylcholine, and, following oxidation to
betaine, choline functions as a methyl group donor in a pathway that produces S-adenosylmethionine. As a methyl donor
choline influences DNA and histone methylation – two central epigenomic processes that regulate gene expression.
Because the fetus and neonate have high demands for choline, its dietary intake during pregnancy and lactation is
particularly important for normal development of the offspring. Studies in rodents have shown that high choline intake
during gestation improves cognitive function in adulthood and prevents memory decline associated with old age. These
behavioral changes are accompanied by electrophysiological, neuroanatomical, and neurochemical changes and by altered
patterns of expression of multiple cortical and hippocampal genes including those encoding key proteins that contribute to
the biochemical mechanisms of learning and memory. These actions of choline are observed long after the exposure to the
nutrient ended (months) and correlate with fetal hepatic and cerebral cortical choline-evoked changes in global- and genespecific
DNA cytosine methylation and with dramatic changes of the methylation pattern of lysine residues 4, 9 and 27 of
histone H3. Moreover, gestational choline modulates the expression of DNA (Dnmt1, Dnmt3a) and histone
(G9a/Ehmt2/Kmt1c, Suv39h1/Kmt1a) methyltransferases. In addition to the central role of DNA and histone methylation
in brain development, these processes are highly dynamic in adult brain, modulate the expression of genes critical for
synaptic plasticity, and are involved in mechanisms of learning and memory. A recent study documented that in a cohort
of normal elderly people, verbal and visual memory function correlated positively with the amount of dietary choline
consumption. It will be important to determine if these actions of choline on human cognition are mediated by epigenomic
mechanisms or by its influence on acetylcholine or phospholipid synthesis.
