ArticlePloS one2021
The BHMT-betaine methylation pathway epigenetically modulates oligodendrocyte maturation.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
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- Trimethylamine N-oxide and related metabolites may regulate DNA methylation and trigger cardiovascular disease.Clinical epigenetics · 2026Article
- Betaine: A Promising Natural Product for Neurological and Psychiatric Diseases.Current neuropharmacology · 2026Review
- Betaine as a regulator of metabolism, epigenetics, and cellular osmoprotection: therapeutic implications in cardiometabolic and renal diseases.Frontiers in pharmacology · 2026Review
- Newborn Screening Alone Cannot Prevent Most Cases of Severe Vitamin B12 Deficiency in the First Year of Life.Nutrients · 2025Article
- The association between plasma betaine level and brain structural changes in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2025Article
- Identification of methionine metabolism related prognostic model and tumor suppressive functions of BHMT in hepatocellular carcinoma.Scientific reports · 2025Article
- Effect of betaine on growth performance, methionine metabolism, and methyl transfer in broilers aged 1 to 21 days and fed a low-methionine diet.The journal of poultry science · 2025Article
- A Comprehensive Examination of the Role of Epigenetic Factors in Multiple Sclerosis.International journal of molecular sciences · 2024Review
- Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase (G6PD) by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis.Science China. Life sciences · 2024Article
- Beneficial Effects ofNutrients · 2024Review
- Investigation of ferroptosis-associated molecular subtypes and immunological characteristics in lupus nephritis based on artificial neural network learning.Arthritis research & therapy · 2024Article
- Molecular Mechanisms Provide a Landscape for Biomarker Selection for Schizophrenia and Schizoaffective Psychosis.International journal of molecular sciences · 2023Review
- A metabolome atlas of mouse brain on the global metabolic signature dynamics following short-term fasting.Signal transduction and targeted therapy · 2023Article
- Bushen-Yizhi formula ameliorates mitochondrial dysfunction and oxidative stress via AMPK/Sirt1 signaling pathway in D-gal-induced aging rats.Chinese medicine · 2023Article
- COVID-19 and Diarylamidines: The Parasitic Connection.International journal of molecular sciences · 2023Review
- mJournal of animal science and biotechnology · 2022Article
- Implications of trimethylamine N-oxide (TMAO) and Betaine in Human Health: Beyond Being Osmoprotective Compounds.Frontiers in molecular biosciences · 2022Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Research into the epigenome is of growing importance as a loss of epigenetic control has been implicated in the development of neurodegenerative diseases. Previous studies have implicated aberrant DNA and histone methylation in multiple sclerosis (MS) disease pathogenesis. We have previously reported that the methyl donor betaine is depleted in MS and is linked to changes in histone H3 trimethylation (H3K4me3) in neurons. We have also shown that betaine increases histone methyltransferase activity by activating chromatin bound betaine homocysteine S-methyltransferase (BHMT). Here, we investigated the role of the BHMT-betaine methylation pathway in oligodendrocytes. Immunocytochemistry in the human MO3.13 cell line, primary rat oligodendrocytes, and tissue from MS postmortem brain confirmed the presence of the BHMT enzyme in the nucleus in oligodendrocytes. BHMT expression is increased 2-fold following oxidative insult, and qRT-PCR demonstrated that betaine can promote an increase in expression of oligodendrocyte maturation genes SOX10 and NKX-2.2 under oxidative conditions. Chromatin fractionation provided evidence of a direct interaction of BHMT on chromatin and co-IP analysis indicates an interaction between BHMT and DNMT3a. Our data show that both histone and DNA methyltransferase activity are increased following betaine administration. Betaine effects were shown to be dependent on BHMT expression following siRNA knockdown of BHMT. This is the first report of BHMT expression in oligodendrocytes and suggests that betaine acts through BHMT to modulate histone and DNA methyltransferase activity on chromatin. These data suggest that methyl donor availability can impact epigenetic changes and maturation in oligodendrocytes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.