Epigenetic reprogramming is a developmental process involving both genome-wide DNA demethylation and chromatin remodelling. Under physiological conditions it occurs at distinct stages of normal embryonic development. However, under in vitro conditions induction of this process can restore pluripotency in somatic cells, and in aberrant situations a similar dedifferentiation process can initiate carcinogenesis. While the kinetics of the reprogramming that occurs in the course of normal development has been well documented, initial steps inducing this process and how DNA methylation marks are removed in vivo remain elusive. The involvement of DNA repair mechanisms in DNA demethylation during epigenetic reprogramming has been recently suggested. The presented project proposes to investigate the upstream events initiating epigenetic reprogramming by using both in vivo and in vitro approaches. We will focus on recently discovered candidates involved in 5-methylcytosine hydroxylation and will investigate a possible involvement of this modification of 5-methylcytosine in the epigenetic reprogramming during mouse development. We will also examine the potential repair enzymes able to remove this epigenetic mark in order to highlight other protein partners involved in this process. Data obtained on this pathway will not only enrich our understanding towards developmental reprogramming, but also enhance our ability to manipulate cell fate in vitro.
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