Epigenetic information in the genome is important for normal development and ageing and its deregulation can be associated with various diseases. Epigenetic information is generally stable in differentiated cells in the adult organism, though it degrades during ageing. However in germ cells, early embryos, embryonic stem cells and iPS cells genome-wide reprogramming of epigenetic information takes place. Epigenetic reprogramming is associated with the return of the genome to pluripotency or totipotency, the erasure of epimutations, resetting parental imprints, and possibly the repression of retransposons in the germline. Epigenetic reprogramming is also critical for experimental reprogramming such as cloning by nuclear transfer, cell fusion, and iPS cell generation.
You will be working in an internationally leading lab that studies the mechanisms and functional consequences of epigenetic reprogramming. You will study the molecular pathways of reprogramming especially of demethylation of DNA which includes passive and active demethylation. Passive demethylation can occur by regulation of Dnmt1 and Uhrf1 including by cell signaling principles. Active demethylation occurs by oxidation of methylcytosine (5mC) to 5hmC, 5fC, and 5caC by the TET enzymes or by deamination by AID/APOBEC enzymes. You will be using mouse knockout and cell models, or biochemical approaches, to study these pathways. Our approaches include epigenomics, bioinformatics and cell signalling which you will have the opportunity to engage with, including through the affiliated Single Cell Genomics Centre at the nearby Sanger Institute (http://www.sanger.ac.uk/research/projects/singlecellcentre). The functional consequences of manipulating reprogramming pathways for normal development, ageing, and iPS cell generation will also be investigated. You will be joining an enthusiastic and collaborative team of students and postdocs embedded in one of the largest programmes of Epigenetics and Nuclear Dynamics science within Europe.
- Ficz G, Hore TA, Santos F, Lee HJ, Dean W, Arand J, Krueger F, Oxley D, Paul YL, Walter J, Cook SJ, Andrews S, Branco MR & Reik W (2013) FGF signalling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency. Cell Stem Cell 13: 351-359
- Seisenberger S, Andrews S, Krueger F, Arand J, Walter J, Santos F, Popp C, Thienpont B, Dean W & Reik W (2012) The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell 48: 849-862
- Ficz G, Branco MR, Seisenberger S, Santos F, Krueger F, Hore TA, Marques CJ, Andrews S & Reik W (2011) Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 473: 398-402
- Popp C, Dean W, Feng S, Cokus SJ, Andrews S, Pellegrini M, Jacobsen SE & Reik W (2010) Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature 463: 1101-1105