Mechanism of Gene Expression Reprogramming during Meiotic Maturation and Pre-Implantation Development

During meiosis and fertilization, gene expression in differentiated gametes is reprogrammed to allow the initiation of a new program from the totipotent zygotic genome. This remarkable transformation entails the deletion of the maternal and paternal gene expression profiles before or just after fertilization. Although reprogramming of gene expression plays an important role in relaying the genome to the next generation, the molecular mechanism of reprogramming remains unknown. Recently, cloned animals were generated in several species by transferring the nuclei of somatic cells into enucleated metaphase II (MII) oocytes [1–8]. The success of these experiments demonstrates that the MII oocyte cytoplasm has the ability to reprogram gene expression, but there is little information on the molecular events in the genome of the transferred nucleus during the reprogramming process. During reprogramming, the gene expression patterns in the differentiated oocytes should be erased, thereby establishing a totipotent gene expression pattern for fu r ther deve lopment . On the o ther hand , the discrimination of the paternal and maternal genomes should be maintained during genome reprogramming, s ince the paterna l and materna l genomes are functionally asymmetric in mammals. In this review, we describe our recent findings on the changes in the epigenetic modifications of differentiated genomes of oocytes during meiosis, and of somatic nuclei after transfer into oocytes, with special emphasis on the mechanism underlying the reprogramming of gene expression. We highlight two aspects of gene expression in the differentiated oocytes. The first involves erasure of information, and the second involves retention of information during meiosis and fertilization, while gene expression is reprogrammed. Some potential applications of these new findings are discussed.