Imprinting by DNA methylation: from transgenes to endogenous gene sequences.

A number of transgenes in the mouse show variation in methylation and expression phenotypes dependent on parental transmission. It appears that there exist at least two types of transgene imprinting; one is retained on an essentially homozygous background, while the other requires heterozygosity at some modifying loci in the genome and is observed as differences in phenotype in reciprocal crosses. For this type of imprinting to occur, the parental origin of the modifier locus itself is important, and parental asymmetry may involve specific interactions between egg cytoplasm and the chromosomes. Based on the identification of 'methylation polymorphism' in the mouse genome, we also show that endogenous gene sequences can undergo imprinting by DNA methylation.