[HTML][HTML] Global reorganization of the nuclear landscape in senescent cells

T Chandra, PA Ewels, S Schoenfelder… - Cell reports, 2015 - cell.com
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 …
Summary
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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