TY  - JOUR
A1  - Fernández, Agustín F.
A1  - Bayón, Gustavo F.
A1  - Urdinguio, Rocío G.
A1  - Toraño, Estela G.
A1  - García, María G.
A1  - Carella, Antonella
A1  - Petrus-Reurer, Sandra
A1  - Ferrero, Cecilia
A1  - Martinez-Camblor, Pablo
A1  - Cubillo, Isabel
A1  - García-Castro, Javier
A1  - Delgado-Calle, Jesús
A1  - Pérez-Campo, Flor M.
A1  - Riancho, José A.
A1  - Bueno, Clara
A1  - Menéndez, Pablo
A1  - Mentink, Anouk
A1  - Mareschi, Katia
A1  - Claire, Fabian
A1  - Fagnani, Corrado
A1  - Medda, Emanuela
A1  - Toccaceli, Virgilia
A1  - Brescianini, Sonia
A1  - Moran, Sebastián
A1  - Esteller, Manel
A1  - Stolzing, Alexandra
A1  - de Boer, Jan
A1  - Nisticò, Lorenza
A1  - Stazi, Maria A.
A1  - Fraga, Mario F.
T1  - H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells
Y1  - 2015/01/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 27 
EP  - 40 
DO  - 10.1101/gr.169011.113 
VL  - 25 
IS  - 1 
UR  - http://genome.cshlp.org/content/25/1/27.abstract 
N2  - 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. 
ER  -