DNA-methylation reprogramming during early embryogenesis

• Applicant: Professor Dr. Jörn E. Walter
• Subject Area: Human Genetics
• Term: from 2002 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5370898

In mammals DNA-methylation patterns are reprogrammed genome wide at specific developmental periods to generate cells with a broad developmental potential. One such reprogramming occurs in the germ line when primordial germ cells are widely demethylated at early fetal stages followed by sex specific genome wide de novo methylation at late fetal and postnatal stages. The second reprogramming period is in preimplantation embryos. Here initial genome wide demethylation is followed by de novo methylation around the time of embryo implantation, and coincident with the establishment of the first differentiated cell lineages in the embryo. Epigenetic reprogramming is pivotal, as reprogramming mistakes can affect developmental potential e.g. through epigenetic changes in imprinted genes. Reprogramming also has presumably a crucial role to establish the nuclear totipotency of cloned animals. In the proposed projects we will investigate the mechanisms and timing of reprogramming with the focus on demethylation during the early embryonic and germ cell development. These studies will be performed on two model organisms: the mouse and bovine. By comparing these two organisms we will investigate if the initiation, the degree and the timing of reprogramming is conserved. Finally we will address the molecular mechanisms of active demethylation in the zygote and primordial germ cells.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1129: Epigenetics