The genomic loci of specific human tRNA genes exhibit ageing-related DNA hypermethylation

被引：16

作者：

Acton, Richard J. ^{[1
,2
,3
]}

Yuan, Wei ^{[4
,5
]}

Gao, Fei ^{[6
]}

Xia, Yudong ^{[6
]}

Bourne, Emma ^{[7
]}

Wozniak, Eva ^{[7
]}

Bell, Jordana ^{[4
]}

Lillycrop, Karen ^{[3
]}

Wang, Jun ^{[8
,9
,10
]}

Dennison, Elaine ^{[2
]}

Harvey, Nicholas ^{[2
]}

Mein, Charles A. ^{[7
]}

Spector, Tim D. ^{[4
]}

Hysi, Pirro G. ^{[4
]}

Cooper, Cyrus ^{[2
]}

Bell, Christopher G. ^{[1
]}

机构：

[1] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Charterhouse Sq, London, England

[2] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England

[3] Univ Southampton, Inst Dev Sci, Human Dev & Hlth, Southampton, Hants, England

[4] Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London, England

[5] Inst Canc Res, Sutton, Surrey, England

[6] BGI Shenzhen, Shenzhen, Peoples R China

[7] Queen Mary Univ London, Barts & London Genome Ctr, Blizard Inst, Barts & London Sch Med & Dent, London, England

[8] Shenzhen Digital Life Inst, Shenzhen, Guangdong, Peoples R China

[9] iCarbonX, Zhuhai, Guangdong, Peoples R China

[10] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

基金：

英国惠康基金; 欧洲研究理事会; 英国医学研究理事会;

关键词：

POLYMERASE-III TRANSCRIPTION; COHORT PROFILE; STEM-CELLS; METHYLATION; EXPRESSION; PROTEIN; AGE; TARGET; PROLIFERATION; LOCALIZATION;

D O I：

10.1038/s41467-021-22639-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 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. The epigenome has been shown to change with age, potentially impacting on ageing-related disease. Here the authors investigate the DNA methylation state of the genomic loci of human tRNA and observe enrichment for age-related DNA hypermethylation at tRNA loci.

引用

页数：14

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