IGF2 IMPRINTING DOES NOT REQUIRE ITS OWN DNA METHYLATION OR H19 RNA

Three models have been proposed to explain the imprinting of the mouse Igf2 gene on the maternal chromosome. We ruled out the importance of DNA methylation at Igf2 by showing that silencing of Igf2 accompanying the lass of DNA methylation could be overcome by a mutation at the ne ighboring H19 gene that activates Igf2. By replacing the H19 structura l gene with a protein-coding gene, we have ruled out a role foil H19 R NA In the imprinting of Igf2. This replacement resulted in sporadic ac tivation of the H19 promoter an the paternal chromosome without affect ing the level of expression of Igf2, a finding that is inconsistent wi th strict promoter competition between the genes. We conclude that a t ranscriptional model involving access to a common set of enhancers sha red between Igf2 and H19 is the most likely explanation for Igf2 impri nting,