| dc.contributor.author | Bell, CG | |
| dc.contributor.author | Yuan, W | |
| dc.contributor.author | Gao, F | |
| dc.contributor.author | Xia, Y | |
| dc.contributor.author | Bourne, E | |
| dc.contributor.author | Wozniak, E | |
| dc.contributor.author | Bell, J | |
| dc.contributor.author | Lillycrop, K | |
| dc.contributor.author | Wang, J | |
| dc.contributor.author | Dennison, E | |
| dc.contributor.author | Harvey, N | |
| dc.contributor.author | Mein, C | |
| dc.contributor.author | Spector, T | |
| dc.contributor.author | Hysi, P | |
| dc.contributor.author | Cooper, C | |
| dc.date.accessioned | 2021-04-19T10:22:03Z | |
| dc.date.available | 2021-03-05 | |
| dc.date.available | 2021-04-19T10:22:03Z | |
| dc.identifier.issn | 2041-1723 | |
| dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/71340 | |
| dc.description.abstract | The epigenome has been shown to deteriorate with age, potentially impacting on ageing-related disease. tRNA, while arising from only ~46kb (<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 0 hypomethylating. Validation and replication (450k array & 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. | en_US |
| dc.publisher | Nature Research (part of Springer Nature) | en_US |
| dc.relation.ispartof | Nature Communications | |
| dc.rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | |
| dc.subject | DNA methylation | en_US |
| dc.subject | tRNA | en_US |
| dc.subject | Ageing | en_US |
| dc.subject | Epigenetics | en_US |
| dc.subject | Epigenomics | en_US |
| dc.title | The Genomic Loci of Specific Human tRNA Genes Exhibit Ageing-Related DNA Hypermethylation | en_US |
| dc.type | Article | en_US |
| dc.rights.holder | © 2021, The Author(s). Published by Nature | |
| pubs.notes | Not known | en_US |
| pubs.publication-status | Accepted | en_US |
| dcterms.dateAccepted | 2021-03-05 | |
