Global reorganization of the nuclear landscape in senescent cells.
View / Open Files
Authors
Chandra, Tamir
Schoenfelder, Stefan
Kirschner, Kiistina
Thuret, Jean-Yves
Publication Date
2015-02Journal Title
Cell reports
ISSN
2211-1247
Volume
10
Issue
4
Pages
471-483
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Chandra, T., Ewels, P. A., Schoenfelder, S., Furlan-Magaril, M., Wingett, S. W., Kirschner, K., Thuret, J., et al. (2015). Global reorganization of the nuclear landscape in senescent cells.. Cell reports, 10 (4), 471-483. https://doi.org/10.1016/j.celrep.2014.12.055
Abstract
Cellular senescence has been implicated in tumor suppression, development, and aging and is accompanied by large-scale chromatin rearrangements, forming senescence-associated heterochromatic foci (SAHF). However, how the chromatin is reorganized during SAHF formation is poorly understood. Furthermore, heterochromatin formation in senescence appears to contrast with loss of heterochromatin in Hutchinson-Gilford progeria. We mapped architectural changes in genome organization in cellular senescence using Hi-C. Unexpectedly, we find a dramatic sequence- and lamin-dependent loss of local interactions in heterochromatin. This change in local connectivity resolves the paradox of opposing chromatin changes in senescence and progeria. In addition, we observe a senescence-specific spatial clustering of heterochromatic regions, suggesting a unique second step required for SAHF formation. Comparison of embryonic stem cells (ESCs), somatic cells, and senescent cells shows a unidirectional loss in local chromatin connectivity, suggesting that senescence is an endpoint of the continuous nuclear remodelling process during differentiation.
Keywords
Cell Line, Chromatin, Heterochromatin, Humans, In Situ Hybridization, Fluorescence, Cell Proliferation, Chromatin Assembly and Disassembly, Cellular Senescence
Identifiers
External DOI: https://doi.org/10.1016/j.celrep.2014.12.055
This record's URL: https://www.repository.cam.ac.uk/handle/1810/294636