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

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 lami...

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Vydáno v:Genes & development Ročník 27; číslo 16; s. 1800
Hlavní autoři: Sadaie, Mahito, Salama, Rafik, Carroll, Thomas, Tomimatsu, Kosuke, Chandra, Tamir, Young, Andrew R J, Narita, Masako, Pérez-Mancera, Pedro A, Bennett, Dorothy C, Chong, Heung, Kimura, Hiroshi, Narita, Masashi
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 15.08.2013
Témata:
Cell Line
Cell Nucleus - metabolism
Cells, Cultured
Cellular Senescence - genetics
Chromatin Assembly and Disassembly - genetics
Gene Expression Regulation
Heterochromatin - chemistry
Heterochromatin - metabolism
Histones - metabolism
Lamin Type B - genetics
Lamin Type B - metabolism
Protein Binding
Protein Structure, Tertiary
senescence
Lamin B1
epigenetics
ISSN:1549-5477, 1549-5477
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Shrnutí: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.
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content type line 23
ISSN:1549-5477
1549-5477
DOI:10.1101/gad.217281.113