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Cell Rep. 2015 Feb 3;10(4):471-83. doi: 10.1016/j.celrep.2014.12.055. Epub 2015 Jan 29.

Global reorganization of the nuclear landscape in senescent cells.

Author information

1
Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK; The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK. Electronic address: tamir.chandra@babraham.ac.uk.
2
Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
3
Nuclear Dynamics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
4
Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
5
CEA, iBiTec-S, SBIGeM/CNRS FRE3377 I2BC/Université Paris-Sud, Gif-sur-Yvette 91191, France.
6
Bioinformatics Group, The Babraham Institute, Cambridge CB22 3AT, UK.
7
Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK; The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.

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.

PMID:
25640177
PMCID:
PMC4542308
DOI:
10.1016/j.celrep.2014.12.055
[Indexed for MEDLINE]
Free PMC Article

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