1.
[Effects of arsenic trioxide on Id4 methylation status in bone marrow mononuclear cells and its clinical efficacy for myelodysplastic syndrome].
Shao, X, Lu, R, Guan, X, Liu, J, Zhao, J, Shao, Z, Zhan, Z, Ma, J
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2014;(3):247-50
2.
Effect of 1 year B and D vitamin supplementation on LINE-1 repetitive element methylation in older subjects.
Hübner, U, Geisel, J, Kirsch, SH, Kruse, V, Bodis, M, Klein, C, Herrmann, W, Obeid, R
Clinical chemistry and laboratory medicine. 2013;(3):649-55
Abstract
BACKGROUND Disturbed DNA methylation is causally related to chronic diseases like cancer and atherosclerosis. B vitamins are cofactors required for methyl group synthesis and may therefore affect DNA methylation. Vitamin D has epigenetic effects. We tested if B and D vitamin supplementation has an effect on genomic long interspersed nuclear element-1 (LINE-1) methylation and the metabolites S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). METHODS Fifty subjects (median age 68.0 years) were supplemented with a daily oral dose of B vitamins (500 µg folic acid, 500 µg vitamin B12 and 50 mg vitamin B6), 1200 IU vitamin D and 456 mg calcium. Fasting blood samples were collected before and after 1 year of supplementation. LINE-1 methylation was determined in genomic DNA from blood cells as a surrogate for whole genome methylation. In addition, SAM, SAH and total homocysteine (tHcy) were measured in plasma samples. RESULTS Plasma homocysteine decreased significantly after supplementation (12.8 vs. 9.1 µmol/L; p<0.05), whereas SAM, SAH, the SAM/SAH ratio and LINE-1 methylation did not change significantly. LINE-1 methylation was not significantly correlated with SAH, homocysteine or B vitamins. CONCLUSIONS Long-term vitamin B supplementation had no effect on LINE-1 methylation in blood cells nor on plasma levels of SAM and SAH. Vitamin B and D supplementation seems to have no effect on DNA methylation, especially in cases where no severe deficiency exists.
3.
Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia.
Ingrosso, D, Cimmino, A, Perna, AF, Masella, L, De Santo, NG, De Bonis, ML, Vacca, M, D'Esposito, M, D'Urso, M, Galletti, P, et al
Lancet (London, England). 2003;(9370):1693-9
Abstract
BACKGROUND Hyperhomocysteinaemia occurs in several genetically determined and acquired disorders and is highly prevalent in patients with uraemia. In these disorders, homocysteine precursor S-adenosylhomocysteine, a powerful competitive inhibitor of S-adenosylmethionine-dependent methyltransferases, is increased, suggesting unbalanced methylation. We aimed to investigate whether DNA hypomethylation is present in patients with uraemia who also have hyperhomocysteinaemia and whether regulation of specific classes of genes, dependent on DNA methylation, is compromised. METHODS We selected men with hyperhomocysteinaemia and uraemia who were having standard haemodialysis treatment, and compared them with healthy male controls. We measured the homocysteine concentration from plasma samples and obtained DNA and RNA samples from peripheral mononuclear cells. DNA methylation was assessed by cytosine extension assay and by Southern blotting. Allelic expression of pseudoautosomal and imprinted genes was investigated by analysis of suitable restriction fragment length polymorphisms. FINDINGS Total DNA hypomethylation was higher in patients than in controls (z score -4.593, p=0.0006) and allelic expression was changed in both sex-linked and imprinted genes. The shift from monoallelic to biallelic expression was dependent on homocysteine concentrations. Folate therapy, a common method to reduce hyperhomocysteinaemia, restored DNA methylation to normal levels and corrected the patterns of gene expression. INTERPRETATION Our results suggest that hyperhomocysteinaemia affects epigenetic control of gene expression, which can be reverted by folate treatment. Our data support the hypothesis that the toxic action of homocysteine can be mediated by macromolecule hypomethylation.