Genomic imprinting is a parent of origin-dependent gene silencing that
involves marking of alleles in the germline and differential expression
in somatic cells of the offspring. Imprinted genes and abnormal
imprinting have been implicated in development, human disease, and
embryonic stem cell transplantation. We have established a model system
for genomic imprinting using pluripotent 8.5 d.p.c. mouse embryonic germ
(EG) cell lines derived from an interspecific cross. We find that
allele-specific imprinted gene expression has been lost in these cells.
However, partial restoration of allele-specific silencing can occur for
some imprinted genes after in vitro differentiation of EG cells into
somatic cell lineages, indicating the presence of a gametic memory that
is separable from allele-specific gene silencing. We have also generated
a library containing most methylated CpG islands. A subset of these
clones was analyzed and revealed a subdivision of methylated CpG islands
into 4 distinct subtypes: CpG islands belonging to high copy number
repeat families; unique CpG islands methylated in all tissues; unique
methylated CpG islands that are unmethylated in the paternal germline;
and unique CpG islands methylated in tumors. This approach identifies a
methylome of methylated CpG islands throughout the genome.