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Redistribution of the Lamin B1 genomic binding profile affects rearrangement of heterochromatic domains and SAHF formation during senescence.

Sadaie, M; Salama, R; Carroll, T; Tomimatsu, K; Chandra, T; Young, ARJ; Narita, M; Pérez-Mancera, PA; Bennett, DC; Chong, H; et al. Sadaie, M; Salama, R; Carroll, T; Tomimatsu, K; Chandra, T; Young, ARJ; Narita, M; Pérez-Mancera, PA; Bennett, DC; Chong, H; Kimura, H; Narita, M (2013) Redistribution of the Lamin B1 genomic binding profile affects rearrangement of heterochromatic domains and SAHF formation during senescence. Genes Dev, 27 (16). pp. 1800-1808. ISSN 1549-5477 https://doi.org/10.1101/gad.217281.113
SGUL Authors: Bennett, Dorothy Catherine

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Abstract

Senescence is a stress-responsive form of stable cell cycle exit. Senescent cells have a distinct gene expression profile, which is often accompanied by the spatial redistribution of heterochromatin into senescence-associated heterochromatic foci (SAHFs). Studying a key component of the nuclear lamina lamin B1 (LMNB1), we report dynamic alterations in its genomic profile and their implications for SAHF formation and gene regulation during senescence. Genome-wide mapping reveals that LMNB1 is depleted during senescence, preferentially from the central regions of lamina-associated domains (LADs), which are enriched for Lys9 trimethylation on histone H3 (H3K9me3). LMNB1 knockdown facilitates the spatial relocalization of perinuclear H3K9me3-positive heterochromatin, thus promoting SAHF formation, which could be inhibited by ectopic LMNB1 expression. Furthermore, despite the global reduction in LMNB1 protein levels, LMNB1 binding increases during senescence in a small subset of gene-rich regions where H3K27me3 also increases and gene expression becomes repressed. These results suggest that LMNB1 may contribute to senescence in at least two ways due to its uneven genome-wide redistribution: first, through the spatial reorganization of chromatin and, second, through gene repression.

Item Type: Article
Additional Information: This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
Keywords: Lamin B1, epigenetics, senescence, Cell Aging, Cell Line, Cell Nucleus, Cells, Cultured, Chromatin Assembly and Disassembly, Gene Expression Regulation, Heterochromatin, Histones, Lamin Type B, Protein Binding, Protein Structure, Tertiary, Cells, Cultured, Cell Line, Cell Nucleus, Heterochromatin, Histones, Lamin Type B, Cell Aging, Chromatin Assembly and Disassembly, Gene Expression Regulation, Protein Structure, Tertiary, Protein Binding, Lamin B1, senescence, epigenetics, Science & Technology, Life Sciences & Biomedicine, Cell Biology, Developmental Biology, Genetics & Heredity, CELL BIOLOGY, DEVELOPMENTAL BIOLOGY, GENETICS & HEREDITY, Lamin B1, senescence, epigenetics, SET ENRICHMENT ANALYSIS, NUCLEAR LAMINA, CELLULAR SENESCENCE, HUMAN-CELLS, STEM-CELLS, PROTEIN, CHROMATIN, DIFFERENTIATION, ACCUMULATION, ORGANIZATION, Developmental Biology, 06 Biological Sciences, 11 Medical And Health Sciences, 17 Psychology And Cognitive Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: Genes Dev
ISSN: 1549-5477
Language: eng
Dates:
DateEvent
15 August 2013Published
22 July 2013Accepted
Publisher License: Creative Commons: Attribution-Noncommercial 3.0
Projects:
Project IDFunderFunder ID
UNSPECIFIEDCancer Research UKUNSPECIFIED
PubMed ID: 23964094
Web of Science ID: WOS:000323416000006
Go to PubMed abstract
URI: http://sgultest.da.ulcc.ac.uk/id/eprint/108946
Publisher's version: https://doi.org/10.1101/gad.217281.113

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