Impact of extracellular folate levels on global gene expression.

Jhaveri MS, Wagner C, Trepel JB
Mol Pharmacol. 2001 60 (6): 1288-95

PMID: 11723236 · DOI:10.1124/mol.60.6.1288

Methylation of DNA is associated with gene silencing. DNA methylation uses S-adenosylmethionine (SAM) as the methyl donor and the formation of SAM requires a continuous supply of folate from the extracellular milieu. Low extracellular folate levels are known to result in induction of expression of the human alpha folate receptor in nasopharyngeal epidermoid carcinoma cells. Low folate levels have been implicated in global activation of gene expression. We have investigated the impact of lowering the level of extracellular folate by performing cDNA microarray analysis of global gene expression in human nasopharyngeal carcinoma KB cells grown in folate-deplete and folate-replete medium. We found that expression of only eight genes reproducibly responded to variation of folate levels. Among those, three were up-regulated and five were down-regulated. Examination of one gene, H-cadherin, demonstrated down-regulation in response to folate depletion. Despite the low level of extracellular folate, there was hypermethylation of H-cadherin 5' sequences. These data indicate that low extracellular folate positively and negatively influences the expression levels of a small cohort of genes. The data suggest that folate deficiency is associated with gene-specific methylation/demethylation, rather than global DNA demethylation and transcriptional activation.

MeSH Terms (14)

Cadherins Carrier Proteins CpG Islands DNA Methylation Folate Receptors, GPI-Anchored Folic Acid Gene Expression Regulation Humans KB Cells Promoter Regions, Genetic Receptors, Cell Surface RNA, Messenger S-Adenosylhomocysteine S-Adenosylmethionine

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