Linked Life Data

18694733

Source:http://linkedlifedata.com/resource/pubmed/id/18694733

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2008-10-20
pubmed:abstractText
The maintenance of the cellular epigenomic landscape, which depends on the status of the one-carbon metabolic pathway, is essential for normal central nervous system development and function. In the present study, we examined the epigenetic alterations in the brains of Fisher 344 rats induced by the long-term administration of a diet lacking of essential one-carbon nutrients, methionine, choline, and folic acid. The results demonstrated that feeding a folate/methyl-deficient diet causes global DNA hypermethylation as indicated by an increase of genomic 5-methyl-2'-deoxycytidine (5mdC) content and more importantly, by an increase of methylation within unmethylated CpG-rich DNA domains. Interestingly, these epigenetic changes were opposite to those observed in the livers of the same folate/methyl-deficient rats. The hypermethylation changes were associated with an increased protein expression of de novo DNA methyltransferase DNMT3a and methyl-CpG-binding protein 2. Additionally, the gene expression profiling identified 33 significantly up- or down-regulated genes (fold change > or =1.5 and p< or =0.05) in the brains of rats fed a folate/methyl-deficient diet for 36 weeks. Interestingly, we detected an up-regulation of regulatory factor X, 3 (Rfx3) gene, a sequence-specific DNA-binding protein, that mediates the transcriptional activation of silenced by methylation genes, which may be an adaptive protective brain response to hypermethylation. Together, these data suggest that the proper maintenance of the epigenomic landscape in normal brain depends on the adequate supply of essential nutrients involved in the metabolism of methyl groups.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
1237
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25-34
pubmed:dateRevised
2011-9-22
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Epigenetic alterations in the brains of Fisher 344 rats induced by long-term administration of folate/methyl-deficient diet.
pubmed:affiliation
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA. igor.pogribny@fda.hhs.gov
pubmed:publicationType
Journal Article