DMMC Course: EPIGENETICS: FROM MECHANISMS TO MEDICINES

0840-0930 Monday 25 June 2007. O’Reilly Hall, University College Dublin.

Mechanisms and functions of epigenetic reprogramming in mammalian development
Prof Wolf Reik (The Babraham Institute, Cambridge UK)

Mammalian development is characterised by cycles of epigenetic reprogramming which occur in germ cells and early embryos. Epigenetic reprogramming is associated with the erasure of imprints, genetic conflict, and the return of the embryonic genome to totipotency. We are particularly interested in reprogramming of DNA methylation, which may involve active demethylation. We have carried out a genome wide screen of promoter methylation patterns in germ cells, pluripotent tissues, and differentiated cell types. Initial results from this screen begin to reveal the genome wide dynamics of reprogramming associated with the pluripotent state. We are also interested in gaining insights into the mechanisms of active demethylation during reprogramming. We can show that deaminases of the Aid/Apobec family when targeted to a methylated region in vivo can lead to demethylation without incurring sequence mutations. Thus future work is aimed at examining the role of DNA repair pathways in active demethylation.