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Publication : DNA methylation-mediated control of Sry gene expression in mouse gonadal development.

First Author  Nishino K Year  2004
Journal  J Biol Chem Volume  279
Issue  21 Pages  22306-13
PubMed ID  14978045 Mgi Jnum  J:90693
Mgi Id  MGI:3044476 Doi  10.1074/jbc.M309513200
Citation  Nishino K, et al. (2004) DNA methylation-mediated control of Sry gene expression in mouse gonadal development. J Biol Chem 279(21):22306-13
abstractText  DNA methylation at CpG sequences is involved in tissue-specific and developmentally regulated gene expression. The Sry (sex-determining region on the Y chromosome) gene encodes a master protein for initiating testis differentiation in mammals, and its expression is restricted to gonadal somatic cells at 10.5-12.5 days post-coitum (dpc) in the mouse. We found that in vitro methylation of the 5'-flanking region of the Sry gene caused suppression of reporter activity, implying that Sry gene expression could be regulated by DNA methylation-mediated gene silencing. Bisulfite restriction mapping and sodium bisulfite sequencing revealed that the 5'-flanking region of the Sry gene was hypermethylated in the 8.5-dpc embryos in which the Sry gene was not expressed. Importantly, this region was specifically hypomethylated in the gonad at 11.5 dpc, while the hypermethylated status was maintained in tissues that do not express the Sry gene. We concluded that expression of the Sry gene is under the control of an epigenetic mechanism mediated by DNA methylation.
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