Epigenetic mechanisms in health and disease - Associate Faculty group

Adrian Bird's Associate Faculty group studies the way chemical marking of chromosomes affects the activity of the genome in normal and diseased cells.

Epigenetic marks are small chemical groups added to the genome that change the way it is read. To understand their biological role, the group will map the the marks across the genome in normal and diseased cells. Then regions of the genome with unusual marking will be studied further, using animal models to test their functional significance.

[Christoph Bock (Max Planck Institute for Informatics), Wikimedia Commons]

Background

Genetic information encoded by human genome is read selectively in different types of cell. One way in which selectivity is facilitated is by regional marking the chromosome by addition of small chemical moieties.

DNA methylation, for example, facilitates long-term silencing of genes nearby. Patterns of DNA methylation across the genome can at last be deciphered using high-throughput DNA sequencing. This provides an opportunity to understand the logic of epigenetic marking in normal and abnormal cells.

Cancer is largely due to changes in the DNA base sequence, but DNA methylation is often abnormal in tumours too. This may contribute to the disease, for example by silencing genes inappropriately. Now that genome-wide mapping of DNA methylation is possible, this phenomenon can be studied more deeply.

Research

Cancer cell lines have been characterised by the Cancer Genome Project in unprecedented detail. Patterns of genome-wide methylation will be mapped in these same cell lines using recently developed and emerging methodologies based on high-throughput DNA sequencing platforms.

Abnormal DNA methylation in cancer often coincides with regions near genes called 'CpG islands' whose role in normal cells is incompletely understood. Functional annotation of CpG islands that are remote from genes will be undertaken using animal models.

Collaborations

The team is working closely with two groups at the Sanger Institute:

  • Cancer Genome Project - on epigenome mapping of cancer cell lines
  • Mouse Genomics - on genetic ablation of orphan CpG islands

Selected Publications

  • Cell type-specific DNA methylation at intragenic CpG islands in the immune system.

    Deaton AM, Webb S, Kerr AR, Illingworth RS, Guy J, Andrews R and Bird A

    Genome research 2011;21;7;1074-86

    PUBMED: 21628449; PMC: 3129250; DOI: 10.1101/gr.118703.110

  • Orphan CpG islands identify numerous conserved promoters in the mammalian genome.

    Illingworth RS, Gruenewald-Schneider U, Webb S, Kerr AR, James KD, Turner DJ, Smith C, Harrison DJ, Andrews R and Bird AP

    PLoS genetics 2010;6;9

    PUBMED: 20885785; PMC: 2944787; DOI: 10.1371/journal.pgen.1001134

  • CpG islands influence chromatin structure via the CpG-binding protein Cfp1.

    Thomson JP, Skene PJ, Selfridge J, Clouaire T, Guy J, Webb S, Kerr AR, Deaton A, Andrews R, James KD, Turner DJ, Illingworth R and Bird A

    Nature 2010;464;7291;1082-6

    PUBMED: 20393567; DOI: 10.1038/nature08924

  • Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state.

    Skene PJ, Illingworth RS, Webb S, Kerr AR, James KD, Turner DJ, Andrews R and Bird AP

    Molecular cell 2010;37;4;457-68

    PUBMED: 20188665; DOI: 10.1016/j.molcel.2010.01.030

  • A novel CpG island set identifies tissue-specific methylation at developmental gene loci.

    Illingworth R, Kerr A, Desousa D, Jørgensen H, Ellis P, Stalker J, Jackson D, Clee C, Plumb R, Rogers J, Humphray S, Cox T, Langford C and Bird A

    PLoS biology 2008;6;1;e22

    PUBMED: 18232738; PMC: 2214817; DOI: 10.1371/journal.pbio.0060022

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