Loughborough University
Genome Research AFFernandez 2014-27.full.pdf (1.45 MB)

H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells

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posted on 2015-02-25, 14:32 authored by Agustin F. Fernandez, Gustavo F. Bayon, Rocio G. Urdinguio, Estela G. Torano, Maria G. Garcia, Antonella Carella, Sandra Petrus-Reurer, Cecilia Ferrero, Pablo Martinez-Camblor, Isabel Cubillo, Javier Garcia-Castro, Jesus Delgado-Calle, Flor M. Perez-Campo, Jose A. Riancho, Clara Bueno, Pablo Menendez, Anouk Mentink, Katia Mareschi, Fabian Claire, Corrado Fagnani, Emanuela Medda, Virgilia Toccaceli, Sonia Brescianini, Sebastian Moran, Manel Esteller, Alexandra StolzingAlexandra Stolzing, Jan de Boer, Lorenza Nistico, Maria A. Stazi, Maria F. Fraga
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.



  • Mechanical, Electrical and Manufacturing Engineering

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27 - 40 (14)


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


Cold Spring Harbor Press / © The Authors


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This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/by-nc/4.0/

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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/.




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