Highlight Publication July 2007

Farthing CR, Ficz G, Ng RK, Chan C-F, Andrews S, Dean WL, Hemberger M, Reik W (2008)
Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes.
PLoS Genetics 4 e1000116
http://dx.doi.org/10.1371/journal/pgen.1000116

Lay description

Large scale epigenetic reprogramming occurs in mammalian germ cells and the early embryo. The biological purpose of this reprogramming is largely unknown, although it has been suggested that it may be required for the embryonic genome to return to a pluripotent state. We have carried out a genome wide screen of promoter methylation in the mouse, comparing germ cells with pluripotent cells, multipotent cells, and more differentiated cell types. We find that promoter methylation is an epigenetic signature of developmental potency. Genes linked to pluripotency are generally hypomethylated in stem cells and hypermethylated (and silenced) in more differentiated cell types (and our genome wide screen provides new candidates for the regulation of pluripotency). Importantly, germ cells resemble pluripotent cell types in that most promoters have been reprogrammed. However, a small group of key pluripotency regulators (including Nanog), are methylated in mature germ cells, presumably in order to suppress pluripotency at critical stages of germ cell differentiation. Methylation in these genes becomes indeed reprogrammed after fertilisation so that the embryo can regain totipotency. This work therefore shows for the first time that epigenetic reprogramming is crucial for maintaining the pluripotency of germ and embryonic stem cells. The work is funded by a grant from the Technology Strategy Board in collaboration with CellCentric, a company focussed on promising new epigenetic ways of treating diseases such as cancer.

#About the joint lead authors

Cassandra Farthing

After obtaining her first degree in Natural Sciences from Cambridge, Cassandra started her research career at the Wellcome Trust Centre for Human Genetics in Oxford investigating the genetic aspects of congenital heart defects. Shifting fields to epigenetics, Cassandra has been working in Wolf Reik’s lab alongside Gabriella Ficz on reprogramming related projects with a focus on DNA methylation. Recently Cassandra has begun a business fellowship working with BBT Ltd. to promote the Institute’s research within commercial settings.

Gabriella Ficz

Gabriella Ficz earned her Biochemistry degree at the “Al. I. Cuza” University in Iasi, Romania and was enrolled at the International MSc/PhD program for Molecular Biology in Goettingen, Germany. Her PhD research described the biophysical aspects of factors involved in maintenance of cellular identity (the Polycomb Group proteins) and the impact of protein dynamics within the nucleus on gene expression.

Ray Ng

Ray obtained his undergraduate and MPhil degrees in the Chinese University of Hong Kong, then pursued a PhD in the University of Cambridge with Prof. John Gurdon in the Wellcome Trust Gurdon Institute on investigation of epigenetic regulation in animal development. Ray then joined Wolf Reik’s group in the Institute with a Fellowship from the Croucher Foundation, Hong Kong, to study how epigenetic regulation affects embryo stem cell fate. He is also appointed as a Bye-Fellow in Christ’s College at the University of Cambridge.

Simon Andrews

Simon Andrews completed a first degree in Microbiology at the University of Warwick before moving on to do a PhD in molecular evolution at Newcastle University.  He then left bench work behind to pursue his interest in bioinformatics.  He initially worked at the central BBSRC IT Services before moving to Babraham in 2000 to join the bioinformatics support group.