The Netherlands Cancer Institute
We are studying the mechanisms involved in genomic imprinting in the mouse using the mouse insulin-like growth factor type 2 receptor (Igf2r), a maternally expressed gene, as a model.
Work in our lab using YAC transgenic constructs has demonstrated that maternal-specific expression of lgf2r is dependent upon region 2, a CpG-rich region within intron 2 which is methylated on the maternal chromosome (1). In these transgenic experiments, expression of a novel paternally expressed antisense RNA, termed Air (for Antisense Igf2r RNA), was shown to depend upon the unmethylated region 2 on the paternal chromosome.
Region 2 thus acts in cis to repress Igf2r expression. The model we propose is that Igf2r and Air interact by expression competition that may involve the antisense RNA itself.
As a basis for understanding the imprinting mechanism, we have sequenced 138 kb containing Igf2r/Air. This has enabled us to determine the organization of the Air transcript, and the sequence is being used to help identify other features common to imprinted regions of the genome.