Recent studies have revealed that maternal and paternal alleles of som
e imprinted genes are differentially expressed from the earliest time
of expression, with virtually no expression from one of the two allele
s, while for other imprinted genes the normally silent allele can be t
ranscribed during early development. In addition, a number of imprinte
d genes manifest their imprints only in select tissues. These observat
ions indicate that the marks that denote parental chromosome origin ne
ed not directly determine allele expression, but rather bias later epi
genetic modifications toward a particular allele. Thus, factors expres
sed at specific stages or in specific cell types are required to silen
ce 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 modificati
ons are mediated and regulated will be essential for understanding how
genomic imprinting leads to differences in parental allele expression
.