Conservation of Aging and Cancer Epigenetic Signatures across Human and Mouse

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. Although many...

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Detalles Bibliográficos
Autores: Pérez, Raúl F.|||0000-0003-4336-9898, Tejedor, Juan Ramón|||0000-0002-4061-9698, Santamarina-Ojeda, Pablo|||0000-0002-7439-8467, Martínez, Virginia López, Urdinguio, Rocío G.|||0000-0003-2736-5758, Villamañán, Lucía, Candiota Silveira, Ana Paula|||0000-0002-1523-6505, Sarró, N. mí Vidal, Barradas, Marta, Fernandez-Marcos, Pablo Jose, Serrano, Manuel|||0000-0001-7177-9312, Fernández, Agustín F|||0000-0002-3792-4085, Fraga, Mario|||0000-0001-8450-2603
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:255466
Acceso en línea:https://ddd.uab.cat/record/255466
https://dx.doi.org/urn:doi:10.1093/molbev/msab112
Access Level:acceso abierto
Palabra clave:Epigenetics
DNA methylation
Histone modification
Mouse
Human
Conservation
Descripción
Sumario: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. Although 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 nontumoral 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 toward 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.