Stage-specific and cell type-specific aspects of genomic imprinting effects in mammals

Recent studies have revealed that maternal and paternal alleles of some imprinted genes are differentially expressed from the earliest time of expression, with virtually no expression from one of the two alleles, while for other imprinted genes the normally silent allele can be transcribed during early development. In addition, a number of imprinted genes manifest their imprints only in select tissues. These observations indicate that the marks that denote parental chromosome origin need not directly determine allele expression, but rather bias later epigenetic modifications toward a particular allele. Thus, factors expressed at specific stages or in specific cell types are required to silence one parental allele or another. Stage-dependent and tissue-specific epigenetic modifications include the progressive establishment of the mature adult parental allele-specific DNA methylation patterns. These changes resemble and may share a common mechanistic basis with other epigenetic modifications that occur during development. Understanding the mechanisms by which these post-fertilization epigenetic modifications are mediated and regulated will be essential for understanding how genomic imprinting leads to differences in parental allele expression.