Highlight Publication January 2010

Popp C, Dean WL, Feng S, Cokus SJ, Andrews SR, Pellegrini M, Jacobsen SE, Reik W
Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency
Nature
http://dx.doi.org/10.1038/nature08829

Link to press release relating to this publication

Lay summary

Large scale reprogramming of epigenetic information (such as DNA methylation) occurs normally in cells that will ultimately form germ cells and after fertilisation in early embryos. This probably has to do with resetting  cells to a pluripotent or stem cell state from which embryo development and cell differentiation can occur successfully. It might also be important in order to prevent or regulate the inheritance of epigenetic information that we acquire during our lifetime.

Whole Epigenomes (such as ‘methylomes’) can now be unraveled and understood thanks to Next Generation Sequencing technology, which at Babraham is established as part of our new Epigenomics and Transcriptomics facility.

The work published in Nature was led from Babraham as a collaboration between two teams, one at Babraham (C Popp, W Dean, S Andrews, W Reik) and one at HHMI UCLA (S Feng, S Cokus, M Pellegrini, S Jacobsen). Together these teams unravelled the ‘methylomes’ of primordial germ cells in mice, and discovered that reprogramming, that is erasure of pre-existing methylation patterns, had occurred on a remarkable scale. Only about 7% of the cytosines remained methylated (when in normal cells about 80% are methylated). This defines the extent to which epigenetic inheritance of DNA methylation patterns can occur across generations, and also begins to identify some sequences in the genome (such as transposons) that are more resistant to reprogramming than others.

The collaborative team also tested a particular factor, an enzyme called AID (Activation induced deaminase), that they had implicated in the reprogramming process from previous work. In collaboration with Svend Petersen-Mahrt at CRUK in London they had previously found that AID (which plays important roles in the immune system where it induces mutations in immune defense genes) can chemically modify methylated cytosine in DNA which could potentially lead to its removal. The team carried out ‘methylome’ analyses in mouse germ cells that lacked AID, and found that the erasure process was incomplete. This shows that AID has a role in reprogramming, opening up the intriguing possibility that epigenetic inheritance across generations can be regulated in mammals, perhaps depending on specific environmental conditions in which such inheritance is more beneficial to individuals. In addition, using enzymes such as AID might be useful in strategies in which somatic cells are reprogrammed to stem cells (iPS cells) to the benefit of regenerative medicine.

Career history of Christian Popp

Christian Popp joined the Reik lab in 2005 as a research assistant and started his PhD later that year to investigate  the role of cytidine deaminases in epigenetic reprogramming in the germline. He finished his PhD in 2009 and has remained in the lab as a post-doc to continue his work on Aid and its function in mouse PGC development.