Choline deficiency alters global histone methylation and epigenetic marking at the Rel site of the calbindin 1 gene
Open accessAbstract
Maternal choline availability is essential for fetal neurogenesis. Choline deprivation (CD) causes hypomethylation of specific CpG islands in genes controlling cell cycling in fetal hippocampus. We now report that, in C57BL/6 mice, CD during gestational days 12-17 also altered methylation of the histone H3 in E17 fetal hippocampi. In the ventricular and subventricular zones, monomethyl-lysine 9 of H3 (H3K9me1) was decreased by 25% (P<0.01), and in the pyramidal layer, dimethyl-lysine 9 of H3 (H3K9me2) was decreased by 37% (P<0.05). These changes were region specific and were not observed in whole-brain preparations. Also, the same effects of CD on H3 methylation were observed in E14 neural progenitor cells (NPCs) in culture. Changes in G9a histone methyltransferase might mediate altered H3K9me2,1. Gene expression of G9a was decreased by 80% in CD NPCs (P<0.001). In CD, H3 was hypomethylated upstream of the RE1 binding site in the calbindin 1 promoter, and 1 CpG site within the calbindin1 promoter was hypermethylated. REST binding to RE1 (recruits G9a) was decreased by 45% (P<0.01) in CD. These changes resulted in increased expression of calbindin 1 in CD (260%; P<0.05). Thus, CD modulates histone methylation in NPCs, and this could underlie the observed changes in neurogenesis.
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Diets deficient in choline and betaine directly affect histone and DNA methylation in several animal models.
“Furthermore, diets deficient in choline and betaine were shown to directly affect histone and DNA methylation in a number animal models (Du et al., 2009; Mehedint et al., 2010; Niculescu et al., 2006), suggesting that alterations in exogenous methyl donor availability may have strong effects on cellular epigenetic state and thus contribute to tumorigenesis.”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Mehedint et al., 2010
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The supply of choline is important for fetal progenitor cells
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Alzheimer's disease and epigenetic diet
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Cancer stem cells: potential target for bioactive food components
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Early Life Nutrition and Mental Health: The Role of DNA Methylation
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Nutritional influence on epigenetics and effects on longevity
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Choline and the Brain: An Epigenetic Perspective
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Choline the brain and neurodegeneration insights from epigenetics
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Valuing the Diversity of Research Methods to Advance Nutrition Science
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Early-Life Iron Deficiency Anemia Programs the Hippocampal Epigenomic Landscape
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A Conceptual Framework for Studying and Investing in Precision Nutrition
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The Nutrigenetics and Nutrigenomics of the Dietary Requirement for Choline
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Self-citationOn the Role of Low-Dose Effects and Epigenetics in Toxicology
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The Effect of Choline and Resistance Training on Strength and Lean Mass in Older Adults
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- Authors
- Mehedint, M. G., Niculescu, M. D., Craciunescu, C. N., & Zeisel, S. H.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Zeisel, Steven H.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2009-09-14
- Volume
- 24
- Issue
- 1
- Pages
- 184-195
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- PMC
- PMC2797040
- OpenAlex
- W2070463636
- Cited by
- 167
- References
- 77
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 9 · 2023: 2 · 2022: 13 · 2021: 12 · 2020: 12 · 2019: 11 · 2018: 4 · 2017: 15 · 2016: 11 · 2015: 8 · 2014: 12 · 2013: 7 · 2012: 27
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The FASEB Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AG-09525, DK-55865)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- choline deficiency, histone H3 methylation, H3K9me1, H3K9me2, G9a, rest, neural progenitor cells, fetal hippocampus, neurogenesis, epigenetic regulation, CpG methylation, fetal development
- MeSH terms
- RE1-Silencing Transcription Factor, Animals, Base Sequence, Binding Sites, Cells, Cultured, Choline Deficiency, DNA, Female, Hippocampus, Histones, Methylation, Mice, Inbred C57BL, Mitosis, Models, Biological, Pregnancy, Promoter Regions, Genetic, Histone-Lysine N-Methyltransferase, Repressor Proteins, Apoptosis, CpG Islands, Epigenesis, Genetic, Mice, Embryonic Stem Cells, Calbindins, S100 Calcium Binding Protein G, Calbindin 1
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