Higher Order Chromatin Structure and the Epigenome: Implications for Cancer Research

Adele Murrell
Senior Cancer Research Fellow, Hutchison/MRC Research Centre, Department of Oncology; University of Cambridge

The epigenome both extends and influences the execution of the information held within the genome sequence. All somatic nuclei within an organism hold the same genomic information but their epigenetic profiles are expandable and flexible in order to enable interrelated programs of gene expression and silencing according to the cell type, developmental; stage, sex, age and health of the cell. This expandable epigenome is achieved at the level of chromatin through DNA methylation and histone modifications as well as higher order structures1. We have recently shown that the genome and epigenome may interact such that sequence variation within a gene may influence methylation in cis 2-3. These interactions can also take place over long distances suggesting that chromatin higher order structure may play a role in these interactions. Here I describe the DNA methylation dependent chromatin looping structures within the Igf2-H19 domain that separate the genes into active and silent domains and discuss the factors responsible for holding the structures together 4-5. Chromatin loops as part of the epigenome repertoire are likely to play prominent roles in DNA stability and a transcriptional accessibility and will therefore have bearing on neoplasia.

This work is supported by Cancer Research UK


  1. Murrell A., Rakyan V, and Beck (2005) Human Mol.Genet Suppl 1:R3-R10.

  2. Murrell, A Heeson S , Cooper W, Douglas E, Apostolidou S., Moore G.E Maher E and Reik W (2004) Human Mol Genet 13, 1-9.

  3. Lopes S., Lewis A., Hajkova P., Dean W., Oswald J., Murrell A., Constância M., Bartolomei M., J Walter J.,and Reik W (2003) Human Mol Genet 12: 295-305

  4. Weber M, Hagege H, Murrell A, Brunel C, Reik W, Cathala G, Forne T. (2003). Mol Cell Biol. 23, 8953-8959.

  5. Murrell A., Heeson S, and Reik (2004). Nat Genet. 36,(8) 889-893.