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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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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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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DOI: https://doi.org/10.1038/ng1909