Epigenetic reprogramming - Associate Faculty group

Wolf Reik's Associate Faculty group studies how processes that add additional information to the genome (known as epigenetics) enable reprogramming in stem cells and disease.

Epigenetic marks in DNA (such as methylation) are reprogrammed on a genome-wide scale in germ cells and early embryos. This allows the gene expression controls on the genome to be wiped clean and new controls to be introduced to allow differentiation into adult cells. Understanding this reprogramming at a mechanistic level and mapping DNA modifications by sequencing will help with understanding how stem cells function and how epigenetic regulation goes awry in cancer.

[Dr Fatima Santos, Dr Wendy Dean and Professor Wolf Reik, The Babraham Institute]

Background

Epigenetic information in the genome (based on DNA or histone modifications) is relatively stable in somatic tissues but is reprogrammed genome-wide in germ cells and early embryos. This is important in order to remove parental imprints, to create pluripotent stem cells, to erase acquired epimutations, and to control transposons.

The mechanisms of erasing DNA methylation patterns in the genome are beginning to be understood; they involve further modifications of methylcytosine by deamination or hydroxylation resulting in novel DNA modifications (such as hydroxymethylcytosine) that may be intermediates in the process of demethylation, or create new epigenetic signals in their own right.

Novel sequencing methods are being developed that can elucidate the patterns of these new modifications in the genome.

Research

As part of the EU BLUEPRINT project we are developing novel sequencing methods for DNA modifications.

We will apply these as well as our mechanistic insights into epigenetic reprogramming to the study of well characterised cancer cell lines, stem cells and iPS (induced-pluripotent) cells.

Collaborations

We will be working closely with a number of Sanger Institute researchers, faculty and associate faculty members:

  • Cancer Genome Project - on cancer epigenomes
  • Epigenetics in health and disease - on cancer epigenomes
  • Mouse genomics - on iPS cells
  • Mouse developmental genetics and ES cell mutagenesis - on iPS cells
  • Sequencing technology - on new sequencing methods to detect epigenetic modifications

Selected Publications

  • The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells.

    Seisenberger S, Andrews S, Krueger F, Arand J, Walter J, Santos F, Popp C, Thienpont B, Dean W and Reik W

    Molecular cell 2012;48;6;849-62

    PUBMED: 23219530; PMC: 3533687; DOI: 10.1016/j.molcel.2012.11.001

* quick link - http://q.sanger.ac.uk/qwk0n6j9