(A) Mouse Peg3 imprinted domain. The 500-kb imprinted domain contains 7 genes, which are indicated by arrows. Paternally expressed Peg3, Usp29, Zfp264, APeg3 are indicated by the corresponding gene names with blue font, whereas the maternally expressed Zim1, Zim2, Zim3 are indicated by the corresponding gene names with red font. The 4-kb Peg3-DMR controls the imprinting of the entire domain, which is indicated by a grey box (nucleotide positions 6,718,442–6,733,840 in the mouse chromosome 7 of mm10). In contrast, the alternative U1 promoter is known to target de novo DNA methylation to the maternal allele of the Peg3-DMR. This alternative promoter is localized 20-kb upstream of the Peg3-DMR, indicated with a small arrow (nucleotide positions 6,750,937–6,751,933 in the mouse chromosome 7 of mm10). (B) Deletion of the paternal allele of the Peg3-DMR abolishes the transcription of two paternally expressed genes, Peg3 and Usp29, and consequently causes the reactivation of the paternal Zim1. (C) Deletion of the U1 promoter during oogenesis results in the reactivation of two paternally expressed genes, Peg3 and Usp29, from the maternal allele, and subsequently causes significant down-regulation of the maternal Zim1.