The process of epigenetic reprogramming requires global resetting of epigenetic memory at the level of DNA methylation and chromatin modifications. This process leads to major shifts in gene expression profile and can lead to a change in cell fate.||In mammals, under physiological conditions epigenetic reprogramming occurs in the course of development and potentially to some extent also as a part of the regenerative processes during wound healing. Aberrantly, similar processes that reverse cell fate decisions might be partially recapitulated during cellular dedifferentiation observed in cancer. ||In vitro, several reprogramming systems have been described that could be used to revert somatic cell phenotype and to regenerate pluripotency: somatic cell nuclear transfer (SCNT), generation of induced pluripotent cells (iPS), cell fusion or permeabilisation of cells followed by incubation with protein extracts - amongst others.||However, these in vitro reprogramming systems are very inefficient, show high degree of variability and often generate cells with intermediate phenotypes. In order to gain deep mechanistic insights into the molecular processes underlying epigenetic reprogramming we decided to focus on the naturally occurring reprogramming that operates very efficiently in the course of embryonic development. Detailed understanding of these processes can add to our ability to efficiently reprogramme cells in vitro.||Our lab uses mouse zygotes and developing germ line (primordial germ cells PGCs) as in vivo models where epigenetic reprogramming occurs naturally in vivo. The germ line carries unique epigenetic properties, since the reprogramming process involves both genome wide DNA demethylation (including erasure of genomic imprints) and chromatin remodelling. In comparison, the reprogramming process in zygotes involves genome wide DNA demethylation that affects only the paternal genome a few hours after fertilisation.||In order to decipher molecular mechanisms underlying the reprogramming processes we concentrate on 2 main areas:||1) Mechanisms underlying DNA demethylation and erasure of genomic imprints|We have previously documented the kinetics of erasure of DNA methylation and genomic imprints during the development of mouse primordial germ cells (Hajkova et al, 2002, Hajkova et al 2008). Based on the kinetics of the process we suggested that DNA demethylation driven through DNA repair pathway is the most likely scenario to operate in germ cells. We are currently testing this hypothesis.||2) Interplay between DNA demethylation and chromatin dynamics ||Besides our efforts to decipher the mechanisms responsible for large scale loss of DNA methylation in germ cells and zygotes, we are particularly interested in the cross-talk and regulation between DNA demethylation and large scale chromatin remodelling.