Open Access
Open access
Genes and Development, volume 27, issue 16, pages 1787-1799

Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape

Shah Parisha P. 1
Donahue Greg 1
Otte Gabriel L 1
Capell Brian C. 1
Nelson David E. 2
Cao Kajia 1
Aggarwala Varun 1
Cruickshanks Hazel A 3
Rai Taranjit Singh 2
Mcbryan Tony 3
Gregory Brian W. 1
Adams P. M. 3
1
 
* University of Pennsylvania.
2
 
2Institute of Cancer Sciences, University of Glasgow, Cancer Research UK Beatson Labs, Glasgow G61 1BD, United Kingdom
3
 
*University of Glasgow.
Publication typeJournal Article
Publication date2013-08-09
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor10.5
ISSN08909369, 15495477
Genetics
Developmental Biology
Abstract
Senescence is a stable proliferation arrest, associated with an altered secretory pathway, thought to promote tumor suppression and tissue aging. While chromatin regulation and lamin B1 down-regulation have been implicated as senescence effectors, functional interactions between them are poorly understood. We compared genome-wide Lys4 trimethylation on histone H3 (H3K4me3) and H3K27me3 distributions between proliferating and senescent human cells and found dramatic differences in senescence, including large-scale domains of H3K4me3- and H3K27me3-enriched "mesas" and H3K27me3-depleted "canyons." Mesas form at lamin B1-associated domains (LADs) in replicative senescence and oncogene-induced senescence and overlap DNA hypomethylation regions in cancer, suggesting that pre-malignant senescent chromatin changes foreshadow epigenetic cancer changes. Hutchinson-Gilford progeria syndrome fibroblasts (mutant lamin A) also show evidence of H3K4me3 mesas, suggesting a link between premature chromatin changes and accelerated cell senescence. Canyons mostly form between LADs and are enriched in genes and enhancers. H3K27me3 loss is correlated with up-regulation of key senescence genes, indicating a link between global chromatin changes and local gene expression regulation. Lamin B1 reduction in proliferating cells triggers senescence and formation of mesas and canyons. Our data illustrate profound chromatin reorganization during senescence and suggest that lamin B1 down-regulation in senescence is a key trigger of global and local chromatin changes that impact gene expression, aging, and cancer.

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Shah P. P. et al. Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape // Genes and Development. 2013. Vol. 27. No. 16. pp. 1787-1799.
GOST all authors (up to 50) Copy
Shah P. P., Donahue G., Otte G. L., Capell B. C., Nelson D. E., Cao K., Aggarwala V., Cruickshanks H. A., Rai T. S., Mcbryan T., Gregory B. W., Adams P. M., Berger S. L. Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape // Genes and Development. 2013. Vol. 27. No. 16. pp. 1787-1799.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1101/gad.223834.113
UR - https://doi.org/10.1101%2Fgad.223834.113
TI - Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape
T2 - Genes and Development
AU - Shah, Parisha P.
AU - Donahue, Greg
AU - Otte, Gabriel L
AU - Capell, Brian C.
AU - Nelson, David E.
AU - Cao, Kajia
AU - Aggarwala, Varun
AU - Cruickshanks, Hazel A
AU - Rai, Taranjit Singh
AU - Mcbryan, Tony
AU - Gregory, Brian W.
AU - Adams, P. M.
AU - Berger, Shelley L.
PY - 2013
DA - 2013/08/09 00:00:00
PB - Cold Spring Harbor Laboratory
SP - 1787-1799
IS - 16
VL - 27
PMID - 23934658
SN - 0890-9369
SN - 1549-5477
ER -
BibTex |
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BibTex Copy
@article{2013_Shah
author = {Parisha P. Shah and Greg Donahue and Gabriel L Otte and Brian C. Capell and David E. Nelson and Kajia Cao and Varun Aggarwala and Hazel A Cruickshanks and Taranjit Singh Rai and Tony Mcbryan and Brian W. Gregory and P. M. Adams and Shelley L. Berger},
title = {Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape},
journal = {Genes and Development},
year = {2013},
volume = {27},
publisher = {Cold Spring Harbor Laboratory},
month = {aug},
url = {https://doi.org/10.1101%2Fgad.223834.113},
number = {16},
pages = {1787--1799},
doi = {10.1101/gad.223834.113}
}
MLA
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MLA Copy
Shah, Parisha P., et al. “Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape.” Genes and Development, vol. 27, no. 16, Aug. 2013, pp. 1787-1799. https://doi.org/10.1101%2Fgad.223834.113.
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