Parent-specific methylation reprogramming in early embryos: implications for mammalian development and embryo biotechnology

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Our aim is a better understanding of the functional significance of genome-wide opposing patterns in paternal and maternal DNA methylation during preimplantation development. We will analyze the evolutionary conservation of differential demethylation of the paternal and maternal genomes in representative mammalian (mouse, cattle, pig, rabbit) and lower vertebrate species (medaka, zebrafish) as well as the frequency and consequences of disturbed methylation reprogramming in mouse embryos from normal matings and in vitro production. Our experiments will show whether abnormal methylation patterns in mammalian embryos contribute to the high incidence of early pregnancy failure. Since methylation reprogramming defects may also have important implications for mammalian cloning, we will analyze the methylation patterns in cloned rabbit embryos, using different nuclear transfer protocols and embryo culture systems. In addition, we will study the higher-order nuclear organization of imprinted gene clusters, which are protected from genome-wide demethylation during preimplantation development. We assume that a specific functional architecture of the early embryonic nucleus is important for genomic imprinting and methylation reprogramming.