Chandra, Ewels et al. mapped changes in genome organization in cellular senescence using HiC. Contrary to the believed increase in heterochromatin in senescence associated heterochromatic foci (SAHF) formation, they describe a loss of local interactions in heterochromatic regions. This is in agreement with changes observed in progeria cells.

Cellular senescence has been implicated in tumour suppression, development and ageing, and is accompanied by large scale chromatin rearrangements, forming senescence associated heterochromatic foci (SAHF). However, how the chromatin is reorganised 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. Contrary to expectation, we find a dramatic sequence and lamin dependent loss of local interactions in heterochromatin. This change in local connectivity resolves the paradox of opposite 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. A comparison between ES, somatic and senescent cells shows a unidirectional loss in local chromatin connectivity, suggesting senescence is an end point of the continuous nuclear remodelling process during differentiation.