Global reorganization of the nuclear landscape in senescent cells.
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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
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.
Cell Line, Chromatin, Heterochromatin, Humans, In Situ Hybridization, Fluorescence, Cell Proliferation, Chromatin Assembly and Disassembly, Cellular Senescence
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
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/