2024-03-28T23:06:42Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/106722023-09-28T13:44:58Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2102com_20.500.12105_2052col_20.500.12105_16970col_20.500.12105_16962col_20.500.12105_2103
00925njm 22002777a 4500
dc
Fernandez, Agustín F
author
Bayón, Gustavo F
author
Urdinguio, Rocio G
author
Toraño, Estela G
author
García, María G
author
Carella, Antonella
author
Petrus-Reurer, Sandra
author
Ferrero, Cecilia
author
Martinez-Camblor, Pablo
author
Delgado-Calle, Jesús
author
Pérez-Campo, Flor M
author
Riancho, José A
author
Bueno, Clara
author
Menéndez, Pablo
author
Mentink, Anouk
author
Mareschi, Katia
author
Claire, Fabian
author
Fagnani, Corrado
author
Medda, Emanuela
author
Toccaceli, Virgilia
author
Brescianini, Sonia
author
Moran, Sebastián
author
Esteller, Manel
author
Stolzing, Alexandra
author
de Boer, Jan
author
Nisticò, Lorenza
author
Stazi, Maria A
author
Fraga, Mario F
author
Cubillo, Isabel
author
Garcia-Castro, Javier
author
2015-01
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.
Genome Res . 2015 Jan;25(1):27-40.
http://hdl.handle.net/20.500.12105/10672
25271306
10.1101/gr.169011.113
1549-5469
Genome research
H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells.