Transcription-driven DNA methylation setting on the mouse <i>Peg3</i> locus

The imprinting of the mouse <i>Peg3</i> domain is controlled through the Peg3-DMR, which obtains its maternal-specific DNA methylation during oogenesis. In the current study, we deleted an oocyte-specific alternative promoter, termed U1, which is localized 20 kb upstream of the Peg3-DMR. Deletion of this alternative promoter resulted in complete removal of the maternal-specific DNA methylation on the Peg3-DMR. Consequently, the imprinted genes in the <i>Peg3</i> domain become biallelic in the mutants with maternal transmission of the deletion. Expression levels of the imprinted genes were also affected in the mutants: 2-fold upregulation of <i>Peg3</i> and <i>Usp29</i> and downregulation of <i>Zim1</i> to basal levels. Breeding experiments further indicated under-representation of females among the surviving mutants, a potential sex-biased outcome from the biallelic expression of the <i>Peg3</i> domain. Overall, the results suggest that U1-driven transcription may be required for establishing oocyte-specific DNA methylation on the <i>Peg3</i> domain.