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

Buxton, Jessica L., Suderman, Matthew, Pappas, Jane J., Borghol, Nada, McArdle, Wendy, Blakemore, Alexandra I. F., Hertzman, Clyde, Power, Christine, Szyf, Moshe and Pembrey, Marcus (2014) Human leukocyte telomere length is associated with DNA methylation levels in multiple subtelomeric and imprinted loci. Scientific Reports, 4(4954), ISSN (online) 2045-2322

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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.

Item Type: Article
Additional Information: This work was supported by the Canadian Institute for Health Research [grant number: MOP-42411] and the Wellcome Trust [grant numbers 072937/Z/03/Z and WT088431MA].
Research Area: Biological sciences
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing (until 2017) > School of Life Sciences
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Depositing User: Jessica Buxton
Date Deposited: 11 Dec 2017 10:46
Last Modified: 11 Dec 2017 14:12
DOI: https://doi.org/10.1038/srep04954
URI: http://eprints.kingston.ac.uk/id/eprint/40222

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