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Open Access Highly Accessed Research

Tissue-specific variation in DNA methylation levels along human chromosome 1

Cecilia De Bustos18, Edward Ramos239, Janet M Young2, Robert K Tran104, Uwe Menzel1, Cordelia F Langford5, Evan E Eichler36, Li Hsu7, Steve Henikoff46, Jan P Dumanski1 and Barbara J Trask23*

  • * Corresponding author: Barbara J Trask btrask@fhcrc.org

  • † Equal contributors

Author Affiliations

1 Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

2 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

3 Department of Genome Sciences, University of Washington, Seattle, Washington, USA

4 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

5 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

6 Howard Hughes Medical Institute, Seattle, Washington, USA

7 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

8 Current address: United Nations World Food Programme, Lima, Peru

9 Current address: National Institutes of Health, Bethesda Maryland, USA

10 Current address: Genome Center, University of California at Davis, Davis, California, USA

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Epigenetics & Chromatin 2009, 2:7  doi:10.1186/1756-8935-2-7

Published: 8 June 2009

Abstract

Background

DNA methylation is a major epigenetic modification important for regulating gene expression and suppressing spurious transcription. Most methods to scan the genome in different tissues for differentially methylated sites have focused on the methylation of CpGs in CpG islands, which are concentrations of CpGs often associated with gene promoters.

Results

Here, we use a methylation profiling strategy that is predominantly responsive to methylation differences outside of CpG islands. The method compares the yield from two samples of size-selected fragments generated by a methylation-sensitive restriction enzyme. We then profile nine different normal tissues from two human donors relative to spleen using a custom array of genomic clones covering the euchromatic portion of human chromosome 1 and representing 8% of the human genome. We observe gross regional differences in methylation states across chromosome 1 between tissues from the same individual, with the most striking differences detected in the comparison of cerebellum and spleen. Profiles of the same tissue from different donors are strikingly similar, as are the profiles of different lobes of the brain. Comparing our results with published gene expression levels, we find that clones exhibiting extreme ratios reflecting low relative methylation are statistically enriched for genes with high expression ratios, and vice versa, in most pairs of tissues examined.

Conclusion

The varied patterns of methylation differences detected between tissues by our methylation profiling method reinforce the potential functional significance of regional differences in methylation levels outside of CpG islands.