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Long interspersed nucleotide element‐1 hypomethylation in folate‐deficient mouse embryonic stem cells
Author(s) -
Chang Shaoyan,
Wang Li,
Guan Yunqian,
Shangguan Shaofang,
Du Qingan,
Wang Yang,
Zhang Ting,
Zhang Yu
Publication year - 2013
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24496
Subject(s) - methylation , homocysteine , dna methylation , biology , hyperhomocysteinemia , microbiology and biotechnology , biochemistry , chemistry , gene expression , gene
Folate is thought to contribute to health and development by methylation regulation. Long interspersed nucleotide element‐1 (LINE‐1), which is regulated by methylation modification, plays an important role in sculpting the structure and function of genomes. Some studies have shown that folate concentration is related to LINE‐1 methylation. However, the direct association between LINE‐1 methylation and folate deficiency remains unclear. To explore whether folate deficiency directly induced LINE‐1 hypomethylation and to analyze the relationship between folate concentration and the LINE‐1 methylation level, mouse ESCs were treated with various concentrations of folate which was measured by chemiluminescent immunoassay, and the homocysteine content was detected by ELISA. LINE‐1 methylation was examined by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry at various time points. Concurrently, cell proliferation and differentiation were observed. The result showed that the intracellular folate decreases under folate‐deficient condition, conversely, homocysteine content increased gradually and there was a negatively correlated between them. Folate insufficiency induced LINE‐1 hypomethylation at the lowest levels in folate‐free group and moderate in folate‐deficient group, compared with that in the folate‐normal group at day 18. Moreover, LINE‐1 methylation level was positively correlated with folate content, and negatively correlated with homocysteine content. At corresponding time points, proliferation and differentiation of mouse ESCs showed no alteration in all groups. Our data indicated that folate deficiency affected the homeostasis of folate‐mediated one‐carbon metabolism, leading to reduced LINE‐1 methylation in mouse ESCs. This study provides preliminary evidence of folate deficiency affecting early embryonic development. J. Cell. Biochem. 114: 1549–1558, 2013. © 2013 Wiley Periodicals, Inc.