Abstract
DNA methylation is an epigenetic mark that is critical in determining chromatin accessibility and regulating gene expression. This epigenetic mechanism has an important role in T-cell function. We used genome-wide methylation profiling to characterize the DNA methylome in primary human CD4+ T cells. We found that only 5% of CpG islands are methylated in CD4+ T cells, and that DNA methylation peak density is increased in subtelomeric chromosomal regions. We also found an inverse relationship between methylation peak density and chromosomal length. Our data indicate that DNA methylation in gene promoter regions is not always a repressive epigenetic mark. Indeed, about 27% of methylated genes are actively expressed in CD4+ T cells. We demonstrate that repressive methylation peaks are located closer to the transcription start site (TSS) compared with functionally non-repressive peaks (−893±110 bp versus −1342±218 bp (mean±s.e.m.), P-value <0.05). We also show that both a larger number and an increased CpG island density in promoter sequences predict transcriptional permissiveness of DNA methylation. TSS in the majority of genes with permissive DNA methylation peaks is in DNase I hypersensitive sites, indicating a failure of DNA methylation to induce chromatin inaccessibility in these loci.
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Acknowledgements
This work was supported by the National Institute of Health Grant number P20-RR015577 from the National Center for Research Resources, Grant number R03AI076729 from the National Institute of Allergy and Infectious Diseases, the Oklahoma Rheumatic Disease Research Core Centers; the Department of Veterans Affairs; the University of Oklahoma Health Sciences Center; the Oklahoma Medical Research Foundation. The authors thank Dr J Donald Capra, MD, for his critical review of this paper.
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Hughes, T., Webb, R., Fei, Y. et al. DNA methylome in human CD4+ T cells identifies transcriptionally repressive and non-repressive methylation peaks. Genes Immun 11, 554–560 (2010). https://doi.org/10.1038/gene.2010.24
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DOI: https://doi.org/10.1038/gene.2010.24
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