H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells [twins]
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ABSTRACT: In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone posttranslational 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 obtained from individuals aged 2 to 92 identified 18735 hypermethylated and 45407 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 non-genetic 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. Total DNA isolated by standard procedures from peripheral blood of 24 samples obtained from 12 pairs of MZ twins aged 21 to 66.
ORGANISM(S): Homo sapiens
SUBMITTER:
Sonia Brescianini Rocío G Urdinguio Agustin F Fernandez Lorenza Nisticò Manel Esteller Anouk Mentink Sebastián Moran Maria G Garcia Flor M Perez-Campo Katia Mareschi Corrado Fagnani Jan de Boer Pablo Menendez Mario F Fraga Isabel Cubillo Maria A Stazi Jesús Delgado-Calle Clara Bueno Antonella Carella Gustavo F Bayón Javier García-Castro José A Riancho Alexandra Stolzing Fabian Claire Pablo Martinez-Camblor Cecilia Ferrero Estela G Toraño Sandra Petrus-Reurer Virgilia Toccaceli Emanuela Medda
PROVIDER: E-GEOD-52113 | ArrayExpress | 2014-09-25
SECONDARY ACCESSION(S): GSE52113PRJNA226710
REPOSITORIES: GEO, ArrayExpress
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