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DNA methylation profiling of human chromosomes 6, 20 and 22

Nature Genetics volume 38, pages 1378–1385 (2006)Cite this article

Abstract

DNA methylation is the most stable type of epigenetic modification modulating the transcriptional plasticity of mammalian genomes. Using bisulfite DNA sequencing, we report high-resolution methylation profiles of human chromosomes 6, 20 and 22, providing a resource of about 1.9 million CpG methylation values derived from 12 different tissues. Analysis of six annotation categories showed that evolutionarily conserved regions are the predominant sites for differential DNA methylation and that a core region surrounding the transcriptional start site is an informative surrogate for promoter methylation. We find that 17% of the 873 analyzed genes are differentially methylated in their 5′ UTRs and that about one-third of the differentially methylated 5′ UTRs are inversely correlated with transcription. Despite the fact that our study controlled for factors reported to affect DNA methylation such as sex and age, we did not find any significant attributable effects. Our data suggest DNA methylation to be ontogenetically more stable than previously thought.

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Figure 1: Type and distribution of amplicons.
Figure 2: Amplicon coverage in the context of gene and CpG island annotation, as shown for a 1-Mb region on chromosome 22q12.2.
Figure 3: Correlation of DNA methylation with spatial distance and cell type.
Figure 4: CpG methylation at transcription start sites (TSSs).
Figure 5: Global DNA methylation, age and sex.
Figure 6: Analysis of T-DMRs.
Figure 7: Conservation of methylation between human and mouse orthologous amplicons.

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Acknowledgements

We thank E. Calautti for his advice on culturing of keratinocytes, A. Meyerhans for critical reading of the manuscript, J. Maass for her help obtaining tissue samples and K. Fischer for his support providing genomic annotations. F.E. thanks Y.-S. Kim for many discussions. V.K.R. was supported by a C.J. Martin Fellowship from the National Health and Medical Research Council of Australia. J.A., J.B., T.C., R.D., T.A.D., R.H., K.H., D.K.J., J.L., D.N., R.P., T.W., J.R. and S.B. were supported by the Wellcome Trust.

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  1. Jan Kunde

    Present address: Schering AG, Müllerstr. 178, 13342, Berlin, Germany

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  1. Epigenomics AG, Kleine Präsidentstrasse 1, Berlin, 10178, Germany

    Florian Eckhardt, Joern Lewin, Rene Cortese, Matthias Burger, Carolina Haefliger, Jan Kunde, Christoph Koenig, Thomas Otto, Stefanie Seemann, Christian Thompson, Alex Olek & Kurt Berlin

  2. Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, Cambridge, UK

    Vardhman K Rakyan, John Attwood, John Burton, Tony V Cox, Rob Davies, Thomas A Down, Roger Horton, Kevin Howe, David K Jackson, Jennifer Liddle, David Niblett, Roger Pettett, Tony West, Jane Rogers & Stephan Beck

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Correspondence to Florian Eckhardt or Stephan Beck.

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Competing interests

S.B. is a member of the scientific advisory board of Epigenomics AG. K.B. and A.O. are founders of Epigenomics AG, A.O. is a consultant of this company, and K.B., M.B., R.C., F.E., C.H., C.K., J.K., J.L., T.O. and C.T. are employees of Epigenomics AG.

Supplementary information

Supplementary Fig. 1

Global methylation profiles of chromosomes 6, 20 and 22. (PDF 1082 kb)

Supplementary Fig. 2

Correlation between DNA methylation and CpG density. (PDF 953 kb)

Supplementary Fig. 3

Distinction of imprinting versus mosaicism at heterogeneously methylated loci. (PDF 890 kb)

Supplementary Fig. 4

Methylation of CGI- and non-CGI-containing 5′ UTRs. (PDF 1089 kb)

Supplementary Fig. 5

Cluster analysis of chromosome 22 amplicons. (PDF 987 kb)

Supplementary Fig. 6

Differentially methylated CGIs located within the 5′ UTR. (PDF 427 kb)

Supplementary Table 1

Sample details. (PDF 380 kb)

Supplementary Table 2

Examples of genes found to be differentially methylated. (PDF 552 kb)

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Eckhardt, F., Lewin, J., Cortese, R. et al. DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet 38, 1378–1385 (2006). https://doi.org/10.1038/ng1909

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