SEX-SPECIFIC EXONS CONTROL DNA METHYLTRANSFERASE IN MAMMALIAN GERM-CELLS

The spermatozoon and oocyte genomes bear sex-specific methylation patt erns that are established during gametogenesis and are required for th e allele-specific expression of imprinted genes in somatic tissues. Th e mRNA for Dnmt1, the predominant maintenance and de novo DNA (cytosin e-5)-methyl transferase in mammals, is present at high levels in postm itotic murine germ cells but undergoes alternative splicing of sex-spe cific 5' exons, which controls the production and localization of enzy me during specific stages of gametogenesis. An oocyte-specific 5' exon is associated with the production of very large amounts of active Dnm t1 protein, which is truncated at the N terminus and sequestered in th e cytoplasm during the later stages of oocyte growth, while a spermato cyte-specific 5' exon interferes with translation and prevents product ion of Dnmt1 during the prolonged crossing-over stage of male meiosis. During the course of postnatal oogenesis, Dnmt1 is present at high le vels in nuclei only in growing dictyate oocytes, a stage during which gynogenetic developmental potential is lost and biparental development al potential is gained.