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|Conservation of aging and cancer epigenetic signatures across human and mouse
|Pérez, Raúl F.
Tejedor, Juan Ramón
Santamarina Ojeda, Pablo
López Martínez, Virginia
Urdinguio, Rocío G.
Candiota, Ana Paula
Fernández Marcos, Pablo José
Serrano Marugán, Manuel
Fernández, Agustín F.
Fraga, Mario F.
|Aging and cancer are two interrelated processes, with aging being a major risk factor for the development of cancer. Parallel epigenetic alterations have been described for both, although differences, especially within the DNA hypomethylation scenario, have also been recently reported. While many of these observations arise from the use of mouse models, there is a lack of systematic comparisons of human and mouse epigenetic patterns in the context of disease. However, such comparisons are significant as they allow to establish the extent to which some of the observed similarities or differences arise from pre-existing species-specific epigenetic traits. Here, we have used reduced representation bisulfite sequencing to profile the brain methylomes of young and old, tumoral and non-tumoral brain samples from human and mouse. We first characterized the baseline epigenomic patterns of the species and subsequently focused on the DNA methylation alterations associated with cancer and aging. Next, we described the functional genomic and epigenomic context associated with the alterations, and finally we integrated our data to study interspecies DNA methylation levels at orthologous CpG sites. Globally, we found considerable differences between the characteristics of DNA methylation alterations in cancer and aging in both species. Moreover, we describe robust evidence for the conservation of the specific cancer and aging epigenomic signatures in human and mouse. Our observations point towards the preservation of the functional consequences of these alterations at multiple levels of genomic regulation. Finally, our analyses reveal a role for the genomic context in explaining disease- and species-specific epigenetic traits.© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
|Versió postprint del document publicat a: https://doi.org/10.1093/molbev/msab112
|It is part of:
|Molecular Biology and Evolution, 2021
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|Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
Publicacions de projectes de recerca finançats per la UE
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
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