The Netherlands Cancer Institute
We are studying the imprinted, maternal-specific expression of the mouse insulin-like growth factor type 2 receptor (Igf2r). Recent work in our lab using YAC transgenic constructs has demonstrated that maternal-specific expression of Igf2r is dependent on a CpG island, named region 2, situated within intron 2, which is methylated on the maternal allele but unmethylated on the paternal allele. Deletion of region 2 results in biallelic Igf2r expression. In these transgenic experiments, a novel antisense RNA was shown to be expressed from the unmethylated region 2 on the paternal chromosome, indicating that region 2 may act to repress Igf2r through the action of an antisense RNA. As a basis for understanding how this antisense RNA may act to silence the Igf2r paternal promoter, and also to help identify other key components involved in the imprinting mechanism, we have sequenced 136 kb containing the paternally-expressed antisense Igf2r transcript, termed Air (Antisense Imprintor RNA). EST databases have been used to assemble a partial sequence of the Air RNA, showing that it spans at least 95 kb, and appears to be intronless.