Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1‐carbon metabolism
Autor: | Alexandra M. Binder, Aggeliki Tserga, Karin B. Michels |
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Rok vydání: | 2017 |
Předmět: |
Epigenomics
0301 basic medicine Genotype Placenta Biology Polymorphism Single Nucleotide Biochemistry Andrology Genomic Imprinting 03 medical and health sciences Folic Acid 0302 clinical medicine Insulin-Like Growth Factor II Pregnancy Genetics medicine Humans Epigenetics Imprinting (psychology) Molecular Biology Alleles Methylenetetrahydrofolate Reductase (NADPH2) Research Infant Newborn Methylation DNA Methylation female genital diseases and pregnancy complications Vitamin B 12 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cord blood Methylenetetrahydrofolate reductase embryonic structures DNA methylation biology.protein Female Genomic imprinting Biotechnology |
Zdroj: | The FASEB Journal. 31:5149-5158 |
ISSN: | 1530-6860 0892-6638 |
Popis: | Folic acid is an essential component of 1-carbon metabolism, which generates methyl groups for DNA methylation. Disruption of genomic imprinting leads to biallelic expression which may affect disease susceptibility possibly reflected in high levels of S-adenosyl-homocysteine (SAH) and low levels of S-adenosyl-methionine (SAM). We investigated the association between folic acid supplementation during pregnancy and loss of imprinting (LOI) of IGF2 and H19 genes in placentas and cord blood of 90 mother–child dyads in association with the methylenetetrahydrofolate reductase (MTHFR) genotype. Pyrosequencing was used to evaluate deviation from monoallelic expression among 47 placentas heterozygous for H19 and 37 placentas and cord blood tissues heterozygous for IGF2 and H19 methylation levels of 48 placentas. We detected relaxation of imprinting (ROI) and LOI of H19 in placentas not associated with differences in methylation levels of the H19ICR. Placentas retained monoallelic allele-specific gene expression of IGF2, but 32.4% of cord blood samples displayed LOI of IGF2 and 10.8% showed ROI. High SAH levels were significantly associated with low H19 methylation. An interesting positive association between SAM/SAH ratio and high H19 methylation levels was detected among infants with low B12 levels. Our data suggest profound differences in regulation of imprinting in placenta and cord blood; a lack of correlation of the methylome, transcriptome, and proteome; and a complex regulatory feedback network between free methyl groups and genomic imprinting at birth.—Tserga, A., Binder, A. M., Michels, K. B. Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1-carbon metabolism. |
Databáze: | OpenAIRE |
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