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ID 116751
Author
Rodriguez‑Algarra, Francisco Queen Mary University of London
Seaborne, Robert A. E. Queen Mary University of London
Danson, Amy F. Queen Mary University of London|German Cancer Research Center
Yildizoglu, Selin Queen Mary University of London
Law, Pui Pik Queen Mary University of London|King’s College London
Ahmad, Zakaryya Queen Mary University of London
Maudsley, Victoria A. Queen Mary University of London
Brew, Ama Queen Mary University of London
Holmes, Nadine University of Nottingham
Ochôa, Mateus Queen Mary University of London
Hodgkinson, Alan King’s College London
Marzi, Sarah J. Imperial College London
Pradeepa, Madapura M. Queen Mary University of London
Loose, Matthew University of Nottingham
Holland, Michelle L. King’s College London
Rakyan, Vardhman K. Queen Mary University of London
Content Type
Journal Article
Description
Background: Ribosomal DNA (rDNA) displays substantial inter-individual genetic variation in human and mouse. A systematic analysis of how this variation impacts epigenetic states and expression of the rDNA has thus far not been performed.
Results: Using a combination of long- and short-read sequencing, we establish that 45S rDNA units in the C57BL/6J mouse strain exist as distinct genetic haplotypes that influence the epigenetic state and transcriptional output of any given unit. DNA methylation dynamics at these haplotypes are dichotomous and life-stage specific: at one haplotype, the DNA methylation state is sensitive to the in utero environment, but refractory to post-weaning influences, whereas other haplotypes entropically gain DNA methylation during aging only. On the other hand, individual rDNA units in human show limited evidence of genetic haplotypes, and hence little discernible correlation between genetic and epigenetic states. However, in both species, adjacent units show similar epigenetic profiles, and the overall epigenetic state at rDNA is strongly positively correlated with the total rDNA copy number. Analysis of different mouse inbred strains reveals that in some strains, such as 129S1/SvImJ, the rDNA copy number is only approximately 150 copies per diploid genome and DNA methylation levels are < 5%.
Conclusions: Our work demonstrates that rDNA-associated genetic variation has a considerable influence on rDNA epigenetic state and consequently rRNA expression outcomes. In the future, it will be important to consider the impact of inter-individual rDNA (epi)genetic variation on mammalian phenotypes and diseases.
Journal Title
Genome Biology
ISSN
1474760X
NCID
AA11697266
Publisher
BioMed Central|Springer Nature
Volume
23
Start Page
54
Published Date
2022-02-14
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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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DOI (Published Version)
URL ( Publisher's Version )
FullText File
gb_23_54.pdf 22.5 MB
language
eng
TextVersion
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departments
Institute of Advanced Medical Sciences