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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.





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