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

Koichiro Nishino, Naoko Hattori, Satoshi Tanaka, Kunio Shiota*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

134 Citations (Scopus)


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 postcoitum (dpe) 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.

Original languageEnglish
Pages (from-to)22306-22313
Number of pages8
JournalJournal of Biological Chemistry
Issue number21
Publication statusPublished - 2004 May 21
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


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