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Publication : Epigenetic patterns at the mouse prolyl oligopeptidase gene locus suggest the CpG island in the gene body to be a novel regulator for gene expression.

First Author  Matsubara S Year  2010
Journal  Gene Volume  465
Issue  1-2 Pages  17-29
PubMed ID  20600704 Mgi Jnum  J:162687
Mgi Id  MGI:4819641 Doi  10.1016/j.gene.2010.06.006
Citation  Matsubara S, et al. (2010) Epigenetic patterns at the mouse prolyl oligopeptidase gene locus suggest the CpG island in the gene body to be a novel regulator for gene expression. Gene 465(1-2):17-29
abstractText  Prolyl oligopeptidase (POP) is a widely distributed serine peptidase which hydrolyzes small peptides on the carboxyl side of an internal proline residue. While its physiological role has been intensely studied, the regulatory mechanism of the gene expression is poorly understood. This time we assessed the POP mRNA expression in mouse embryos and tissues related to reproduction and development and found that POP mRNA was highly expressed in the ovarian granulosa cell, placental spongiotrophoblast, and blastocyst embryo. To elucidate the mechanism by which POP expression is regulated, we investigated DNA methylation and histone modification patterns of the two CpG islands (CGIs) found at the mouse POP locus. Whereas the CGI including the POP promoter (CGI-1) was completely hypomethylated in all the tissues examined, DNA methylation level of the CGI in the gene body (CGI-2) was lower in the granulosa cell, placenta, and blastocyst than in the liver. Some specific CpGs in CGI-2 were significantly demethylated in the three tissues. An in vitro reporter analysis indicated that CGI-2 enhanced POP promoter activity and its effect was significantly reduced by DNA methylation. Moreover, histone H3 acetylation and H3K4 methylation levels of CGI-2 were higher in the granulosa cell than liver. The results suggest that the CGI-2 region is a cis-element for the POP gene expression.
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