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Fig. 8. Schematic of the hypothetical mechanism that generates different H3/K9
methylation patterns, so that the different parental origins of genomes are
distinguished during early pre-implantation development. In oocytes, H3/K9
methylase actively catalyzes the protein in the maternal genomes, but not in
the cytoplasmic pool. After fertilization, the methylase is inactivated, and
H3/K9 in the paternal genome, which is incorporated from the cytoplasmic pool,
remains undermethylated. The methylase is still present but inactivated by
proteins that are newly synthesized after fertilization. Thus, asymmetric
H3/K9 methylation is established in the parent genomes. This asymmetric
methylation is maintained until the two-cell stage, because of the lack of
methylase and demethylase activities. However, the methylation level decreases
gradually in a passive fashion after each DNA replication. When the DNA is
replicated, the pre-existing nucleosomal structure is disrupted at the
replication fork, and the core histones are dissociated from the DNA. The
histones from the nucleoplasmic pool are sequestered together with the
histones from the pre-existing nucleosomes, and amalgamate into a single
structure. Thus, in the nascent chromatin, pre-existing histones are diluted
with histones that are incorporated from the nucleoplasm after DNA replication
(Wolffe, 1998). At the
four-cell stage, H3/K9 methylase is activated, and catalyzes the proteins in
the genomes of both parental origins.