Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells

BACKGROUND: Age-associated changes in genomic DNA methylation have been primarily attributed to 5-methylcytosine (5mC). However, the recent discovery of 5-hydroxymethylcytosine (5hmC) suggests that this epigenetic mark might also play a role in the process. METHODS: Here, we analyzed the genome-wide...

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Detalles Bibliográficos
Autores: Toraño, Estela G, Bayón, Gustavo F, del Real, Álvaro, Sierra, Marta I, García, María G, Carella, Antonella, Belmonte, Thalia, Urdinguio, Rocio G, Cubillo, Isabel, Garcia-Castro, Javier, Delgado-Calle, Jesús, Pérez-Campo, Flor M, Riancho, José A, Fraga, Mario F, Fernandez, Agustín F
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/4843
Acceso en línea:http://hdl.handle.net/20.500.12105/4843
Access Level:acceso abierto
Palabra clave:5hmC
MSCs
Aging
Epigenetics
Bone-marrow
Descripción
Sumario:BACKGROUND: Age-associated changes in genomic DNA methylation have been primarily attributed to 5-methylcytosine (5mC). However, the recent discovery of 5-hydroxymethylcytosine (5hmC) suggests that this epigenetic mark might also play a role in the process. METHODS: Here, we analyzed the genome-wide profile of 5hmc in mesenchymal stem cells (MSCs) obtained from bone-marrow donors, aged 2-89 years. RESULTS: We identified 10,685 frequently hydroxymethylated CpG sites in MSCs that were, as in other cell types, significantly associated with low density CpG regions, introns, the histone posttranslational modification H3k4me1 and enhancers. Study of the age-associated changes to 5hmC identified 785 hyper- and 846 hypo-hydroxymethylated CpG sites in the MSCs obtained from older individuals. CONCLUSIONS: DNA hyper-hydroxymethylation in the advanced-age group was associated with loss of 5mC, which suggests that, at specific CpG sites, this epigenetic modification might play a role in DNA methylation changes during lifetime. Since bone-marrow MSCs have many clinical applications, and the fact that the epigenomic alterations in this cell type associated with aging identified in this study could have associated functional effects, the age of donors should be taken into account in clinical settings.

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