Human leukocyte telomere length is associated with DNA methylation levels in multiple subtelomeric and imprinted loci.
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.
1] Section of Investigative Medicine, Department of Medicine, Imperial College London, London W12 0NN, UK [2].
Jessica L
JL
Buxton
1] University of Bristol, Bristol, UK [2] McGill University, Montreal, Quebec, Canada [3].
Matthew
M
Suderman
1] McGill University, Montreal, Quebec, Canada [2] University of Toronto, Toronto, Ontario, Canada.
Jane J
JJ
Pappas
Lebanese International University and Lebanese University, Beirut, Lebanon.
Nada
N
Borghol
University of Bristol, Bristol, UK.
Wendy
W
McArdle
Section of Investigative Medicine, Department of Medicine, Imperial College London, London W12 0NN, UK.
Alexandra I F
AI
Blakemore
1] University of British Columbia, Vancouver, British Columbia, Canada [2].
Clyde
C
Hertzman
UCL Institute of Child Health, London, UK.
Christine
C
Power
McGill University, Montreal, Quebec, Canada.
Moshe
M
Szyf
UCL Institute of Child Health, London, UK.
Marcus
M
Pembrey
D000293:Adolescent; D000328:Adult; D001665:Binding Sites; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D018392:Genomic Imprinting; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins; D015398:Signal Transduction; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*; D059505:Telomere Homeostasis; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site; D055815:Young Adult
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C531063:ZFP57 protein, human