Human leukocyte telomere length is associated with DNA methylation levels in multiple subtelomeric and imprinted loci

Jessica L Buxton, Matthew Suderman, Jane J Pappas, Nada Borghol, Wendy McArdle, Alexandra I F Blakemore, Clyde Hertzman, Christine Power, Moshe Szyf, Marcus Pembrey

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Abstract

In humans, leukocyte telomere length (LTL) is positively correlated with lifespan, and shorter LTL is associated with increased risk of age-related disease. In this study we tested for association between telomere length and methylated cytosine levels. Measurements of mean telomere length and DNA methylation at >450,000 CpG sites were obtained for both blood (N = 24) and EBV-transformed cell-line (N = 36) DNA samples from men aged 44-45 years. We identified 65 gene promoters enriched for CpG sites at which methylation levels are associated with leukocyte telomere length, and 36 gene promoters enriched for CpG sites at which methylation levels are associated with telomere length in DNA from EBV-transformed cell-lines. We observed significant enrichment of positively associated methylated CpG sites in subtelomeric loci (within 4 Mb of the telomere) (P < 0.01), and also at loci in imprinted regions (P < 0.001). Our results pave the way for further investigations to help elucidate the relationships between telomere length, DNA methylation and gene expression in health and disease.

Original languageEnglish
Article number4954
Number of pages8
JournalScientific Reports
Volume4
DOIs
Publication statusPublished - 14 May 2014

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    Buxton, J. L., Suderman, M., Pappas, J. J., Borghol, N., McArdle, W., Blakemore, A. I. F., Hertzman, C., Power, C., Szyf, M., & Pembrey, M. (2014). Human leukocyte telomere length is associated with DNA methylation levels in multiple subtelomeric and imprinted loci. Scientific Reports, 4, [4954]. https://doi.org/10.1038/srep04954