An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs)

  1. Vardhman K. Rakyan1,9,10,
  2. Thomas A. Down2,9,
  3. Natalie P. Thorne3,9,
  4. Paul Flicek4,9,
  5. Eugene Kulesha4,
  6. Stefan Gräf4,
  7. Eleni M. Tomazou5,
  8. Liselotte Bäckdahl6,
  9. Nathan Johnson4,
  10. Marlis Herberth7,
  11. Kevin L. Howe3,
  12. David K. Jackson5,
  13. Marcos M. Miretti5,
  14. Heike Fiegler5,8,
  15. John C. Marioni3,
  16. Ewan Birney4,
  17. Tim J.P. Hubbard5,
  18. Nigel P. Carter5,
  19. Simon Tavaré3, and
  20. Stephan Beck6,10
  1. 1 Institute of Cell and Molecular Science, Barts and the London, London E1 2AT, United Kingdom;
  2. 2 Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QR, United Kingdom;
  3. 3 Department of Oncology, University of Cambridge, Cancer Research UK Cambridge Research Institute, Cambridge CB2 0RE, United Kingdom;
  4. 4 European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, United Kingdom;
  5. 5 Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
  6. 6 UCL Cancer Institute, University College London, London WC1E 6DD, United Kingdom;
  7. 7 Institute of Biotechnology, University of Cambridge, Cambridge CB2 1QT, United Kingdom

  1. ↵9 These authors contributed equally to this work.

Abstract

We report a novel resource (methylation profiles of DNA, or mPod) for human genome-wide tissue-specific DNA methylation profiles. mPod consists of three fully integrated parts, genome-wide DNA methylation reference profiles of 13 normal somatic tissues, placenta, sperm, and an immortalized cell line, a visualization tool that has been integrated with the Ensembl genome browser and a new algorithm for the analysis of immunoprecipitation-based DNA methylation profiles. We demonstrate the utility of our resource by identifying the first comprehensive genome-wide set of tissue-specific differentially methylated regions (tDMRs) that may play a role in cellular identity and the regulation of tissue-specific genome function. We also discuss the implications of our findings with respect to the regulatory potential of regions with varied CpG density, gene expression, transcription factor motifs, gene ontology, and correlation with other epigenetic marks such as histone modifications.

Footnotes

  • ↵8 Present address: Roche Diagnostics Limited, West Sussex RH15 9RY, UK.

  • ↵10 Corresponding authors.

    ↵10 E-mail v.rakyan{at}qmul.ac.uk; fax 44-020-78822186.

    ↵10 E-mail s.beck{at}ucl.ac.uk; fax 44-020-76790815.

  • [Supplemental material is available online at www.genome.org. The array data from this study have been submitted to ArrayExpress under accession no. E-TABM-445.]

  • Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.077479.108.

    • Received February 13, 2008.
    • Accepted June 15, 2008.

  • Freely available online through the Genome Research Open Access option.

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  1. Published in Advance June 24, 2008, doi: 10.1101/gr.077479.108 Genome Res. 18: 1518-1529 Copyright © 2008, Cold Spring Harbor Laboratory Press

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