Epigenetics

Dr Vardhman K Rakyan BSc (Hons), PhD

Research field

If a genome is the ‘book of life', then it is epigenetics that makes the book readable! Epigenetics is the study of cellular mechanisms (e.g. DNA methyaltion and histone modifications) that control heritable gene expression states without changing the underlying DNA sequence. It is well established that epigenetic processes are indispensable for development; indeed multicellularity would not be possible without some form of epigenetic control of genome function. But, one of the most exciting findings in the field of epigenetics in recent times has been the discovery of epigenetic variation between individuals. Remarkably, in some cases these epigenetic variants can be inherited by the offspring i.e. biological inheritance that is not DNA-based. Using an integrative approach of genomics, bioinformatics, functional assays, mouse models, and human cohorts, the overall goals of the lab are to understand (i) how epigenetic mechanisms influence normal development (ii) the generation and impact of inter-individual epigenetic differences on phenotypic outcomes (e.g. complex diseases such as type 1 diabetes) (iii) the transgenerational inheritance of these modifications (iv) the potential implications of these phenomena for our understanding of the basis and evolution of phenotypes.

Key research papers

1 Down TA*, Rakyan VK*  (*joint first authors) et al., (2008) A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis. Nature Biotechnology (in press) 

2 Eckhardt F, Lewin J, Cortese R, Rakyan VK , et al., (2006) DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet. 38(12): 1378-85.

3 Rakyan VK & Beck S. (2006) Epigenetic variation and inheritance in mammals. Curr Opin Genet Dev . 16(6): 573-7.

4 Murrell A, Rakyan VK & Beck S. (2005) From genome to epigenome. Hum Mol Genet. 14 Spec No 1:R3-R10.

5 Rakyan VK , Hildmann T, Novik KL, Lewin J et al., (2004) DNA methylation profiling of the human major histocompatibility complex: a pilot study for the human epigenome project. PLoS Biol . 2(12): e405.

6 Rakyan VK , Chong S, Champ ME, Cuthbert PC, et al., (2003) Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci U S A. 100(5): 2538-43.

7 Rakyan V & Whitelaw E. (2003) Transgenerational epigenetic inheritance. Curr Biol. 13(1):R6.

8 Rakyan VK , Blewitt ME, Druker R, Preis JI & Whitelaw E. (2002) Metastable epialleles in mammals. Trends Genet. 18(7): 348-51.

9 Rakyan VK , Preis J, Morgan HD & Whitelaw E. (2001) The marks, mechanisms and memory of epigenetic states in mammals. Biochem J. 356(Pt 1):1-10.