Epigenetic alterations in the brains of Fisher 344 rats induced by long-term administration of folate/methyl-deficient diet

Deregulation of epigenetic mechanisms, especially the removal of methyl groups, has been associated with neuropathological disorders. Both hyper- and hypomethylation of DNA and histones have been implicated in modified regulation of gene expression. Normal central nervous system development and function, particularly neurogenesis, depend on status of the one-carbon metabolic pathway and therefore intake of essential nutrients like methionine, choline and folic acid. These one-carbon nutrients are involved in the metabolism of methyl groups that are needed in cellular methylation reactions, and are acquired from S-adenosylmethionine, the primary universal donor of methyl groups in mammals.

The present study examines the epigenetic alterations that occur in the brains of rats, resulting from long term exposure to a diet lacking these essential nutrients. DNA hypermethylation of unmethylated GC-rich DNA domains could be found in brains of folate/methyl deficient rats and was linked to an increase in protein expression of de novo DNA methyltransferase DNMT3a and methyl-CpG-binding protein 2 (MeCP2). High MeCP2 levels in the brain are related to the development of several neurological disorders. Further analysis of the gene expression in the brains of folate/methyl-deficient rats revealed significant changes in expression of 33 genes involved in nervous system development and function.  
Therefore this study indispensably indicates the connection between the status of epigenetic modifications and the functioning of the one-carbon metabolic pathway.

Reference:

Pogribny IP, Karpf AR, James SR, et al.: Epigenetic alterations in the brains of Fisher 344 rats induced by long-term administration of folate/methyl-deficient diet, BRAIN RESEARCH,  2008

Dania Schumann