H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells
Fernández, Agustín F. (Universidad de Oviedo)
Fernández Bayón, Gustavo (Universidad de Oviedo)
Urdinguio, Rocío G. (Universidad de Oviedo)
Toraño, Estela G. (Universidad de Oviedo)
García, María G. (Universidad de Oviedo)
Carella, Antonella (Universidad de Oviedo)
Petrus-Reurer, Sandra (Universidad de Oviedo)
Ferrero, Cecilia (Universidad de Oviedo)
Martinez-Camblor, Pablo (Oficina de Investigación Biosanitaria (OIB-FICYT) de Asturias)
Cubillo, Isabel (Instituto de Salud Carlos III)
Garcia-Castro, Javier (Instituto de Salud Carlos III)
Delgado-Calle, Jesús (Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Pérez-Campo, Flor M. (Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Riancho, José A. (Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Bueno, Clara (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Menéndez Bujan, Pablo (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Mentink, Anouk (University of Twente)
Mareschi, Katia (University of Turin)
Claire, Fabian (University of Leipzig)
Fagnani, Corrado (Istituto Superiore di Sanità (Roma, Itàlia))
Medda, Emanuela (Istituto Superiore di Sanità (Roma, Itàlia))
Toccaceli, Virgilia (Istituto Superiore di Sanità (Roma, Itàlia))
Brescianini, Sonia (Istituto Superiore di Sanità (Roma, Itàlia))
Moran, S (Institut d'Investigació Biomèdica de Bellvitge)
Esteller, M (Universitat de Barcelona. Departament de Ciències Fisiològiques II)
Stolzing, Alexandra (Loughborough University)
de Boer, Jan (Maastricht University)
Nisticò, Lorenza (Istituto Superiore di Sanità (Roma, Itàlia))
Stazi, Maria A. (Istituto Superiore di Sanità (Roma, Itàlia))
Fraga, Mario (Universidad de Oviedo)

Date:	2015
Abstract:	In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors.
Grants:	Ministerio de Ciencia e Innovación CP11/00131 Ministerio de Ciencia e Innovación CP07/0059 Ministerio de Ciencia e Innovación PS09/02454 Ministerio de Ciencia e Innovación PI12/01080 Ministerio de Economía y Competitividad SAF2013/ 43065
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Genome research, Vol. 25 (january 2015) , p. 27-40, ISSN 1549-5469

DOI: 10.1101/gr.169011.113
PMID: 25271306

14 p, 1.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Research articles
Articles > Published articles