期刊
CELL REPORTS
卷 10, 期 4, 页码 471-483出版社
CELL PRESS
DOI: 10.1016/j.celrep.2014.12.055
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资金
- BBSRC [BB/K010867/1, BBS/E/B/000C0404]
- Wellcome Trust [095645/Z/11/Z]
- Wellcome Trust [095645/Z/11/Z] Funding Source: Wellcome Trust
- BBSRC [BBS/E/B/000C0400, BBS/E/B/000C0404, BBS/E/B/000C0403] Funding Source: UKRI
- MRC [G0801156] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/B/000C0404, BBS/E/B/000C0403, BBS/E/B/000C0400] Funding Source: researchfish
- Medical Research Council [G0801156] Funding Source: researchfish
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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