The role and regulation of UHRF1 during epigenetic reprogramming (360G-Wellcome-109140_Z_15_A)

During both mouse and human embryonic development there are two waves of global DNA demethylation associated with an increase in developmental potential: firstly during the development of the inner cell mass from the gametes, and secondly during the development of primordial germ cells. Although some of these changes in DNA methylation are correlated with gene expression, it is not understood why this epigenetic reprogramming is consistently so extensive. Until recently it was believed that most of this erasure of DNA methylation occurred actively. However, recent research has revealed that regulation of maintenance methylation accounts for the differing rates of demethylation in different reprogramming contexts. Across the majority of these different contexts, the activity of maintenance methylation is controlled by regulation of UHRF1 protein. This project aims to elucidate the mechanism by which UHRF1 protein is regulated during epigenetic reprogramming, then to use this knowledge to assess the importance of this regulation to the acquisition of pluripotency during mammalian embryonic development. This will improve our understanding of developmental and reproductive health and may even shed light on new or improved methods of reprogramming cells for therapeutic applications.