Table 1.
This is a table that summarizes studies conducted in humans and animal models that showed a link between one-carbon-metabolism-associated micronutrients and methylation.
| Description | Outcomes | References |
|---|---|---|
| Prenatal choline and betaine intake in humans |
Reduction in NTD risk | [26,28,29] |
| Maternal choline supplementation in humans |
Attenuation of the stress axis in offspring Alteration in the methylation of Crh and Nr3c1 in placenta and in cord blood with a decrease in corticosterone levels in cord plasma (n = 29) |
[55] |
| Maternal diet supplementation with folic acid during pregnancy |
Changes in methylation of candidate genes related to brain development in blood samples of newborns (n = 86) with a genome-wide decrease in methylation | [39] |
| Maternal supplementation with folic acid in humans |
Genome-wide decrease in methylation, alteration in the methylation status of genes in the offspring (n = 5841) | [38] |
| Methyl donor intake during early postnatal period (2–3 years) | Higher methylation in buccal cells of males compared to females in children at age 4 with no proven association between methyl donor intake and changes in global methylation (n = 73) | [56] |
| Supplementation of folinic acid in female Rett patients | Improved levels of 5-MTHF in CSF of female patients (n = 4) | [57] |
| Prenatal choline supplementation in alcohol-exposed pregnant rats |
Increase in H3K4me3, decrease in H3K9me2 in β-endorphin-producing neurons in the hypothalamus of exposed offspring with a decrease in Pomc gene methylation and decrease in ACTH and corticosterone levels in the blood |
[58] |
| Choline deficiency at E17 in mice | Decrease in G9a, decrease in H3K9me1 and H3K9me2 in the SVZ and ventricular zone in mice hippocampus with no changes in global levels of histone marks in the mouse fetal brain. Decrease in binding of REST on Calb1 gene promoter with an increase in Calb1 expression in NPC |
[53] |
| Methionine intake in Axd mutant mice | Reduction in NTD | [27] |
| Imbalanced levels of VitB12 and folic acid in pregnant Wistar rats |
Hypermethylation in the cortex of adult offspring | [36] |
| Methyl-balanced diet in mice | Increase in KMT8 expression and cancer prevention in liver |
[44] |
| Folate deficient diet in mice | Increase in H3K4me in liver | [43] |
| Wistar rats fed with HM, LV or HMLV | Increase in homocysteine and SAM in the liver, and decrease in H3R8me2 in the brain | [47] |
| Mice-induced hyperhomocysteinemia | Increase in EZH2, increase in H3K27me3 along Cftr gene promoter and decrease in Cftr expression |
[48] |
| Prolonged methionine deprivation in ESCs/iPSCs | Cellular apoptosis | [42] |
| Methionine deficiency in hESCs | Decrease is SAM levels, decrease in H3K4me3 Impacted differentiation of ESC |
[42] |
| Maternal diet supplementation with methyl donors in viable yellow Agouti mice |
Alteration in the methylation status of IAP and Agouti gene expression and shifting phenotype toward the brown color |
[59] |
| Pregnant rats fed with diet low in methyl donors |
Hypermethylation, increase in H3K9Ace along hepatic GR gene promoter and decrease in DNMT1 expression in the offspring | [60] |
| Maternal diet supplementation with methionine and B vitamins in ES mice |
Normalization in methionine levels in plasma and hippocampus and stress axis in offspring with no changes in global DNA methylation |
[61] |
| Elevated paternal dietary intake of methyl donors in mice |
Changes in Mat2a expression and changes in methylation of Kcnmb2 gene promoter in offspring | [62] |
| Paternal diet deficient in methyl donors in mice (FMCD diet) |
Changes in methylation of PP1 gene promoter in the hippocampus of offspring |
[63] |
Abbreviations: 5-methyltetrathydrofolate (5-MTHF), neural tube defect (NTD), cerebrospinal fluid (CSF), subventricular zone (SVZ), repressor element-1 silencing transcription factor (REST), high in methionine (HM), deficient in B vitamins (LV), fed with both (HMLV), proopiomelanocortin (Pomc), corticotropin-releasing hormone (Crh), cystic fibrosis transmembrane conductance regulator (Cftr), adrenocorticotropin hormone (ACTH), neural progenitor cell (NPC), embryonic day 17 (E17), embryonic stem cell (ESC), induced pluripotent stem cell (iPSC), intracisternal A particle (IAP), glucocorticoid receptor (GR), DNA methyltransferase (DNMT), Enhancer of Zeste Homolog 2 (EZH2), protein phosphatase 1 (PP1), acetylation of histone 3 at lysine 9 (H3k9Ace), trimethylation of histone 3 at lysine 4 (H3K4me3), trimethylation of histone 3 at lysine 27 (H3K27me3), dimethylation of histone 3 at arginine 8 (H3R8me2), axial defect (Axd), BK channel subunit (Kcnmb2), dimethylation of histone 3 at lysine 9 (H3k9me2), monomethylation of histone H3 at lysine 9 (H3K9me1), methionine adenosyltransferase (Mat2), calbindin (calb1), glucocorticoid gene (Nr3c1).