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Replicative senescence is associated with nuclear reorganization and DNA methylation at specific transcription factor binding sites (MBD-seq)

ABSTRACT: Primary cells enter replicative senescence after a limited number of cell divisions. This process is associated with reproducible changes in DNA methylation (DNAm) at specific sites in the genome. The mechanism that drives senescence-associated DNAm changes remains unknown and may arise through drift in DNAm or through regulated, senescence dependent modifications at specific sites in the genome. In this study, we analyzed the reorganization of nuclear architecture and DNA methylation during long-term culture of human fibroblasts and mesenchymal stromal cells (MSCs). [MethylCap-seq] Fibroblasts of two female donors (both 43 years old) were culture expanded and DNA was harvested of 10,000,000 cells at early passage (P3 or P5) and late passage (P30 and P33). DNA methylation changes were subsequently analyzed by MethylCap-Seq.

ORGANISM(S): Homo sapiens

SUBMITTER: Wolfgang Wagner 

PROVIDER: E-GEOD-59960 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Replicative senescence is associated with nuclear reorganization and with DNA methylation at specific transcription factor binding sites.

Hänzelmann Sonja S   Beier Fabian F   Gusmao Eduardo G EG   Koch Carmen M CM   Hummel Sebastian S   Charapitsa Iryna I   Joussen Sylvia S   Benes Vladimir V   Brümmendorf Tim H TH   Reid George G   Costa Ivan G IG   Wagner Wolfgang W  

Clinical epigenetics 20150304

<h4>Background</h4>Primary cells enter replicative senescence after a limited number of cell divisions. This process needs to be considered in cell culture experiments, and it is particularly important for regenerative medicine. Replicative senescence is associated with reproducible changes in DNA methylation (DNAm) at specific sites in the genome. The mechanism that drives senescence-associated DNAm changes remains unknown - it may involve stochastic DNAm drift due to imperfect maintenance of e  ...[more]

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