Global Reorganization of the Nuclear Landscape in Senescent Cells

• Main 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
• Format: Article
• Language: English
• Published: Elsevier 2015-02-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S221112471401122X

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.