Mechanism of the reprogramming of gene expression in mammalian oocytes

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The purpose of this research project is to clarify the mechanism of reprogramming of gene expression in the oocytes before and/or after fertilizaion. Since the gene expression patterns of differentiated cells are maintained by the mechanism of "cell memory" during mitosis and those in the oocytes are reprogrammed into the ones in the totopotent embryos, we postulated that erasing the cell memory is involved in the reprogramming of gene expression by initializing the program.We examined histone acetylations in the oocytes and embryos as a candidate marker of cell memory. Immunocytochemistry with specific antibody against various lysine residues of histories revealed that acetylation of histones was maintained during mitosis in the preimplantaion embryos after fertilization as well as somatic cells but that it disappeared in the oocytes when they resumed meiosis and this deacetylated state was maintained until metaphase II (MII). Since it has been shown that the the gene expression pattern is reprogrammed when the somatic nuclei transferred into MII stage oocytes, we examined histone acetylation in these nuclei. The results showed that all lysine residues examined were deacetylated after transplantation. These results suggested that global histone deacetylation is involved in the reprogramming of gene expression in the oocytes.This meiosis-specific histone deacetylation seemed to be induced by the association of histone deacetylase I (HDAC1) with meiotic chromosomes, since HDAC1 was co-localized with chromosomes during meiosis but not mitosis. Finally, we showed that histone deacetylation is regulated by p34^<cdc2> protein kinase during meiosis.