---
title: "Global Reorganization of the Nuclear Landscape in Senescent Cells"
url: "https://phil.ewels.co.uk/publications/2015/chandra-cell-reports"
site: "phil.ewels.co.uk"
author: "Phil Ewels"
section: "Publications"
journal: "Cell Reports"
published: "2015-02-01"
doi: "https://doi.org/10.1016/j.celrep.2014.12.055"
authors: "Tamir Chandra, Philip Andrew Ewels, Stefan Schoenfelder, Mayra Furlan-Magaril, Steven William Wingett, Kristina Kirschner, Jean-Yves Thuret, Simon Andrews, Peter Fraser, Wolf Reik"
---

# Global Reorganization of the Nuclear Landscape in Senescent Cells

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.

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From the personal website of Phil Ewels, a software developer and bioinformatician in Stockholm, Sweden: https://phil.ewels.co.uk/
The whole site as Markdown: https://phil.ewels.co.uk/llms.txt