Seminar by Petra Hajkova, MRC Clinical Sciences Centre, Imperial College, London

The main focus of our laboratory is the investigation of molecular mechanisms that lead to the erasure of epigenetic memory at both histone and DNA modification level.


Major epigenetic changes are connected with the process of epigenetic reprogramming in vivo and in vitro. The current in vitro reprogramming systems (SCNT, iPS generation, cell fusion) are characterised by very low efficiency and, importantly, inefficient erasure of epigenetic memory at the DNA methylation level has been identified as one of the barriers in these processes (De Carvalho et al.,2010 ; Kim et al., 2010; Polo et al., 2010).


In order to elucidate the underlying molecular mechanisms, we focus on the systems where epigenetic reprogramming occurs naturally as a part of normal embryonic development. There are two instances of genome wide DNA demethylation during mouse development: early postfertilisation zygote and the developing germ line. Despite the considerable efforts of many researchers over many years, the exact mechanism(s) implicated in the loss of 5mC during these developmental processes remain elusive.


We and others have previously reported involvement of Base Excision DNA repair pathway in the active DNA demethylation in the mouse zygotes and germ cells (Hajkova et al, Nature 2008; Hajkova et al, Science 2010, Wossidlo et al, EMBO J 2010). Recently, conversion of 5mC to 5hmC driven by the Tet family of iron dependent oxygenases has been mechanistically linked to the DNA demethylation processes in vitro and in vivo. I will discuss the recent progress in our understanding of these intriguing phenomena.