Establishment of Imprinted Methylation Patterns during Development

Abstract

Genomic imprinting is a classic example of epigenetic control of gene expression in mammals. It represents a process that marks the parental origin of certain genes, resulting in their allele-specific expression. Imprinting, which is implicated in the inequality of the maternal and paternal genomes in mammals, results in the developmental failure of isoparental embryos to develop properly (Surani 1993). An imbalance of specific parental chromosomes in the embryo or aberrant expression of the imprinted genes results in a number of genetic disorders in man and may also contribute to tumor development (Feinberg 1993; Nicholls 1993).

Several model explanations have been proposed for the evolutionary acquisition of genomic imprinting as a developmental control mechanism in mammals (Moore and Haig 1991; Barlow 1993; Varmuza and Mann 1994). One of these models (Moore and Haig 1991) suggests that imprinting might have evolved in mammals because of the conflicting “interests” of maternal and paternal genes within the embryo. This model proposes that paternally expressed genes promote embryonic growth, whereas maternal genes act to restrain the use of maternal resources. A suitable example that corroborates this argument is the paternally expressed Igf2 gene and its counterpart, maternally expressed receptor (Igf2r). The different contribution to the embryonic phenotype of paternal and maternal genes had in fact been demonstrated in parthenogenetic and androgenetic embryos. Although the development of extraembryonic tissues in parthenogenetic embryos harboring two copies of the maternal genome is impaired, the development of the embryo proper is normal. In contrast, the embryo proper in androgenones...