title: Global reorganization of the nuclear landscape in senescent cells.
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.
authors: 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.
authors: Tamir
authors: T
authors: Chandra
authors: Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
authors: Philip Andrew
authors: PA
authors: Ewels
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
authors: Stefan
authors: S
authors: Schoenfelder
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
authors: Mayra
authors: M
authors: Furlan-Magaril
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
authors: Steven William
authors: SW
authors: Wingett
authors: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
authors: Kristina
authors: K
authors: Kirschner
authors: CEA, iBiTec-S, SBIGeM/CNRS FRE3377 I2BC/Université Paris-Sud, Gif-sur-Yvette 91191, France.
authors: Jean-Yves
authors: JY
authors: Thuret
authors: Bioinformatics Group, The Babraham Institute, Cambridge CB22 3AT, UK.
authors: Simon
authors: S
authors: Andrews
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
authors: Peter
authors: P
authors: Fraser
authors: Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK; The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors: Wolf
authors: W
authors: Reik
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence
chemical_list: D002843:Chromatin; D006570:Heterochromatin
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