机构：[1]William Harvey Research Institute, Barts & The London School of Medicine and Dentistry, Charterhouse Square, Queen Mary University of London, London, UK.[2]MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.[3]Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, UK.[4]Department of Twin Research & Genetic Epidemiology, St Thomas Hospital, King’s College London, London, UK.[5]Institute of Cancer Research, Sutton, UK.[6]BGI-Shenzhen, Shenzhen, China.[7]Barts & The London Genome Centre, Blizard Institute, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.[8]Shenzhen Digital Life Institute, Shenzhen, Guangdong, China.[9]iCarbonX, Zhuhai, Guangdong, China.[10]State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
The epigenome has been shown to deteriorate with age, potentially impacting on ageing-related disease. tRNA, while arising from only ˜46 kb (<0.002% genome), is the second most abundant cellular transcript. tRNAs also control metabolic processes known to affect ageing, through core translational and additional regulatory roles. Here, we interrogate the DNA methylation state of the genomic loci of human tRNA. We identify a genomic enrichment for age-related DNA hypermethylation at tRNA loci. Analysis in 4,350 MeDIP-seq peripheral-blood DNA methylomes (16-82 years), identifies 44 and 21 hypermethylating specific tRNAs at study-and genome-wide significance, respectively, contrasting with none hypomethylating. Validation and replication (450k array and independent targeted Bisuphite-sequencing) supported the hypermethylation of this functional unit. Tissue-specificity is a significant driver, although the strongest consistent signals, also independent of major cell-type change, occur in tRNA-iMet-CAT-1-4 and tRNA-Ser-AGA-2-6. This study presents a comprehensive evaluation of the genomic DNA methylation state of human tRNA genes and reveals a discreet hypermethylation with advancing age.
基金：
We gratefully acknowledge the individuals from TwinsUK, Mavidos and the Hertfordshrie
cohort. TwinsUK received funding from the Wellcome Trust (Ref: 081878/Z/06/Z), European
Community’s Seventh Framework Programme (FP7/2007-2013), the National
Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and
Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in
partnership with King’s College London. Further funding support for the EpiTwin project
was obtained from the European Research Council (project number 250157) and BGI. SNP
Genotyping was performed by The Wellcome Trust Sanger Institute and National Eye
Institute via NIH/CIDR. The authors would like to thank Nikki Graham for her assistance
with the identification and pooling of the MAVIDOS and Hertfordshire DNA samples. The
authors also acknowledge the use of the IRIDIS High Performance Computing Facility, and
associated support services at the University of Southampton, in the completion of this
work. The MRC-LEU is supported by the Medical Research Council (MRC). R.J.A. was in
receipt of a MRC Doctoral fund (1820097).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
最新[2025]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
第一作者机构：[1]William Harvey Research Institute, Barts & The London School of Medicine and Dentistry, Charterhouse Square, Queen Mary University of London, London, UK.[2]MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.[3]Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, UK.
通讯作者：
推荐引用方式(GB/T 7714)：
Acton Richard J,Yuan Wei,Gao Fei,et al.The genomic loci of specific human tRNA genes exhibit ageing-related DNA hypermethylation.[J].Nature communications.2021,12(1):2655.doi:10.1038/s41467-021-22639-6.
APA：
Acton Richard J,Yuan Wei,Gao Fei,Xia Yudong,Bourne Emma...&Bell Christopher G.(2021).The genomic loci of specific human tRNA genes exhibit ageing-related DNA hypermethylation..Nature communications,12,(1)
MLA：
Acton Richard J,et al."The genomic loci of specific human tRNA genes exhibit ageing-related DNA hypermethylation.".Nature communications 12..1(2021):2655
综合性期刊