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


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.

SUBMITTER: Buxton JL 

PROVIDER: S-EPMC4344300 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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

Buxton Jessica L JL   Suderman Matthew M   Pappas Jane J JJ   Borghol Nada N   McArdle Wendy W   Blakemore Alexandra I F AI   Hertzman Clyde C   Power Christine C   Szyf Moshe M   Pembrey Marcus M  

Scientific reports 20140514


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 sit  ...[more]

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