Shaoyan Chang and Li Wang contributed equally to this work.
Long interspersed nucleotide element-1 hypomethylation in folate-deficient mouse embryonic stem cells†
Article first published online: 9 MAY 2013
Copyright © 2013 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 7, pages 1549–1558, July 2013
How to Cite
Chang, S., Wang, L., Guan, Y., Shangguan, S., Du, Q., Wang, Y., Zhang, T. and Zhang, Y. (2013), Long interspersed nucleotide element-1 hypomethylation in folate-deficient mouse embryonic stem cells. J. Cell. Biochem., 114: 1549–1558. doi: 10.1002/jcb.24496
- Issue published online: 9 MAY 2013
- Article first published online: 9 MAY 2013
- Accepted manuscript online: 7 JAN 2013 08:48AM EST
- Manuscript Accepted: 18 DEC 2012
- Manuscript Received: 31 JUL 2012
- National Natural Science Fund of China. Grant Numbers: 81000249, 81150008
- Special research projects of health industry “infant malnutrition assessment and intervention”. Grant Number: 201002006
- Young Scientists Research Fund of Beijing Municipal Health Bureau. Grant Number: 2010-2012
- LONG INTERSPERSED NUCLEOTIDE ELEMENTS;
- EMBRYONIC STEM CELLS;
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.