DYNAMIC METHYLATION ADJUSTMENT AND COUNTING AS PART OF IMPRINTING MECHANISMS

Monoallelic expression in diploid mammalian cells appears to be a wide spread phenomenon, with the most studied examples being X-chromosome i nactivation in eutherian female cells and genomic imprinting in the mo use and human, Silencing and methylation of certain sites on one of th e two alleles in somatic cells is specific with respect to parental so urce for imprinted genes and random for X-linked genes, We report here evidence indicating that: (i) differential methylation patterns of im printed genes are not simply copied from the gametes, but rather estab lished gradually after fertilization; (ii) very similar methylation pa tterns are observed for diploid, tetraploid, parthenogenic, and androg enic preimplantation mouse embryos, as well as parthenogenic and andro genic mouse embryonic stem cells; (iii) haploid parthenogenic embryos do not show methylation adjustment as seen in diploid or tetraploid em bryos, but rather retain the maternal pattern, These observations sugg est that differential methylation in imprinted genes is achieved by a dynamic process that senses gene dosage and adjusts methylation simila r to X-chromosome inactivation.