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-...

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Detalles Bibliográficos
Autores: Toraño, Estela G., Bayón, Gustavo F., Real, Álvaro del, Sierra, Marta I., García, María G., Carella, Antonella, Belmonte, Thalia, Urdinguio, Rocío G., Cubillo, Isabel, García-Castro, Javier, Delgado-Calle, Jesús, Pérez-Campo, Flor Maria, Riancho, José A., Fraga, Mario F., Fernández, Agustín F.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/173158
Acceso en línea:http://hdl.handle.net/10261/173158
Access Level:acceso abierto
Palabra clave:Bone marrow
Epigenetics
Aging
MSCs
5hmC
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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