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Title: H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells
Authors: Fernandez, Agustin F.
Bayon, Gustavo F.
Urdinguio, Rocio G.
Torano, Estela G.
Garcia, Maria G.
Carella, Antonella
Petrus-Reurer, Sandra
Ferrero, Cecilia
Martinez-Camblor, Pablo
Cubillo, Isabel
Garcia-Castro, Javier
Delgado-Calle, Jesus
Perez-Campo, Flor M.
Riancho, Jose A.
Bueno, Clara
Menendez, Pablo
Mentink, Anouk
Mareschi, Katia
Claire, Fabian
Fagnani, Corrado
Medda, Emanuela
Toccaceli, Virgilia
Brescianini, Sonia
Moran, Sebastian
Esteller, Manel
Stolzing, Alexandra
de Boer, Jan
Nistico, Lorenza
Stazi, Maria A.
Fraga, Maria F.
Issue Date: 2015
Publisher: Cold Spring Harbor Press / © The Authors
Citation: FERNANDEZ, A.F. ... et al, 2015. H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells. Genome Research, 25 (1), pp.27-40
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.
Description: This paper is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
Version: Accepted for publication
DOI: 10.1101/gr.169011.113
URI: https://dspace.lboro.ac.uk/2134/16811
Publisher Link: http://dx.doi.org/10.1101/gr.169011.113
ISSN: 1088-9051
Appears in Collections:Published Articles (Mechanical, Electrical and Manufacturing Engineering)

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