Global reorganization of the nuclear landscape in senescent cells

Chandra, T., Ewels, P. A., Schoenfelder, S., Furlan-Magaril, M., Wingett, S. W., Kirschner, K. , Thuret, J.-Y., Andrews, S., Fraser, P. and Reik, W. (2015) Global reorganization of the nuclear landscape in senescent cells. Cell Reports, 10(4), pp. 471-483. (doi:10.1016/j.celrep.2014.12.055) (PMID:25640177) (PMCID:PMC4542308)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kirschner, Dr Kristina
Authors: Chandra, T., Ewels, P. A., Schoenfelder, S., Furlan-Magaril, M., Wingett, S. W., Kirschner, K., Thuret, J.-Y., Andrews, S., Fraser, P., and Reik, W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cell Reports
Publisher:Elsevier
ISSN:2211-1247
ISSN (Online):2211-1247
Published Online:29 January 2015
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Cell Reports 10(4):471-483
Publisher Policy:Reproduced under a Creative Commons License

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