Buxton Jessica L, Suderman Matthew, Pappas Jane J, Borghol Nada, McArdle Wendy, Blakemore Alexandra I F, Hertzman Clyde, Power Christine, Szyf Moshe, Pembrey Marcus
1] Section of Investigative Medicine, Department of Medicine, Imperial College London, London W12 0NN, UK [2].
1] University of Bristol, Bristol, UK [2] McGill University, Montreal, Quebec, Canada [3].
Sci Rep. 2014 May 14;4:4954. doi: 10.1038/srep04954.
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.
在人类中，白细胞端粒长度（LTL）与寿命呈正相关，较短的LTL与年龄相关疾病风险增加有关。在本研究中，我们测试了端粒长度与甲基化胞嘧啶水平之间的关联。对44至45岁男性的血液（N = 24）和EBV转化细胞系（N = 36）DNA样本，测量了>450,000个CpG位点的平均端粒长度和DNA甲基化情况。我们鉴定出65个富含CpG位点的基因启动子，其甲基化水平与白细胞端粒长度相关，以及36个富含CpG位点的基因启动子，其甲基化水平与EBV转化细胞系DNA中的端粒长度相关。我们观察到亚端粒区域（端粒4 Mb范围内）（P < 0.01）以及印记区域的位点（P < 0.001）中，正相关甲基化CpG位点显著富集。我们的结果为进一步研究铺平了道路，以帮助阐明健康和疾病中端粒长度、DNA甲基化和基因表达之间的关系。
