Tissue-specific DNA methylation loss during ageing and carcinogenesis is linked to chromosome structure, replication timing and cell division rates
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- dc.contributor.author Dmitrijeva, Marija
- dc.contributor.author Ossowski, Stephan
- dc.contributor.author Serrano Pubull, Luis, 1982-
- dc.contributor.author Schaefer, Martin H.
- dc.date.accessioned 2019-11-26T07:53:58Z
- dc.date.available 2019-11-26T07:53:58Z
- dc.date.issued 2018
- dc.description.abstract DNA methylation is an epigenetic mechanism known to affect gene expression and aberrant DNA methylation patterns have been described in cancer. However, only a small fraction of differential methylation events target genes with a defined role in cancer, raising the question of how aberrant DNA methylation contributes to carcinogenesis. As recently a link has been suggested between methylation patterns arising in ageing and those arising in cancer, we asked which aberrations are unique to cancer and which are the product of normal ageing processes. We therefore compared the methylation patterns between ageing and cancer in multiple tissues. We observed that hypermethylation preferentially occurs in regulatory elements, while hypomethylation is associated with structural features of the chromatin. Specifically, we observed consistent hypomethylation of late-replicating, lamina-associated domains. The extent of hypomethylation was stronger in cancer, but in both ageing and cancer it was proportional to the replication timing of the region and the cell division rate of the tissue. Moreover, cancer patients who displayed more hypomethylation in late-replicating, lamina-associated domains had higher expression of cell division genes. These findings suggest that different cell division rates contribute to tissue- and cancer type-specific DNA methylation profiles.
- dc.description.sponsorship German Research Foundation [SCHA 1933/1-1]; European Union Seventh Framework Programme [FP7/2007-2013] under grant agreements [HEALTH-F4-2011-278568 (PRIMES)]; Spanish Ministry of Economy, Industry and Competitiveness (MEIC) [BFU2015-63571-P] and to the EMBL partnership; the European Regional Development Fund (ERDF/FEDER); Centro de Excelencia Severo Ochoa and the support of the CERCA Programme/Generalitat de Catalunya. Funding for open access charge: Spanish Ministry of Economy, Industry and Competitiveness (MEIC) [BFU2015-63571-P].
- dc.format.mimetype application/pdf
- dc.identifier.citation Dmitrijeva M, Ossowski S, Serrano L, Schaefer MH. Tissue-specific DNA methylation loss during ageing and carcinogenesis is linked to chromosome structure, replication timing and cell division rates. Nucleic Acids Res. 2018;46(14):7022-39. DOI: 10.1093/nar/gky498
- dc.identifier.doi http://dx.doi.org/10.1093/nar/gky498
- dc.identifier.issn 0305-1048
- dc.identifier.uri http://hdl.handle.net/10230/42977
- dc.language.iso eng
- dc.publisher Oxford University Press
- dc.relation.ispartof Nucleic Acids Research. 2018;46(14):7022-39
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/278568
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-63571-P
- dc.rights © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
- dc.title Tissue-specific DNA methylation loss during ageing and carcinogenesis is linked to chromosome structure, replication timing and cell division rates
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion