TY - JOUR
T1 - H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells
AU - Fernandez, Agustin F.
AU - Bayon, Gustavo F.
AU - Urdinguio, Rocio G.
AU - Torano, Estela G.
AU - Garcia, Maria G.
AU - Carella, Antonella
AU - Petrus-Reurer, Sandra
AU - Ferrero, Cecilia
AU - Martinez-Camblor, Pablo
AU - Cubillo, Isabel
AU - Garcia-Castro, Javier
AU - Delgado-Calle, Jesus
AU - Perez-Campo, Flor M.
AU - Riancho, Lose A.
AU - Bueno, Clara
AU - Menendez, Pablo
AU - Mentink, Anouk
AU - Mareschi, Katia
AU - Claire, Fabian
AU - Fagnani, Corrado
AU - Medda, Emanuela
AU - Toccaceli, Virgilia
AU - Brescianini, Sonia
AU - Moran, Sebastian
AU - Esteller, Manel
AU - Stolzing, Alexandra
AU - de Boer, Jan
AU - Nistico, Lorenza
AU - Stazi, Maria A.
AU - Fraga, Mario F.
PY - 2015/1
Y1 - 2015/1
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 ofDNA 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.
AB - 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 ofDNA 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.
U2 - 10.1101/gr.169011.113
DO - 10.1101/gr.169011.113
M3 - Article
C2 - 25271306
SN - 1088-9051
VL - 25
SP - 27
EP - 40
JO - Genome Research
JF - Genome Research
IS - 1
ER -