Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence.
Masashi Narita,Sabrina Nuñez,Sabrina Nuñez,Edith Heard,Masako Narita,Athena W. Lin,Stephen Hearn,David L. Spector,Gregory J. Hannon,Scott W. Lowe +9 more
TLDR
A distinct heterochromatic structure that accumulates in senescent human fibroblasts is described, which is designated senescence-associated heterochROMatic foci (SAHF) and is associated with the stable repression of E2F target genes.About:
This article is published in Cell.The article was published on 2003-06-13 and is currently open access. It has received 2055 citations till now. The article focuses on the topics: Senescence-associated heterochromatin focus & E2F.read more
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Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells
TL;DR: It is demonstrated that AGO2, RB1 and microRNAs (miRNAs), as exemplified here by let-7, physically and functionally interact to repress RB1/E2F-target genes in senescence, and suggested that miRNA/AGO2-mediated SA-TGS may contribute to tumour suppression by stably repressing proliferation-promoting genes in premalignant cancer cells.
Journal ArticleDOI
Biomarkers of cellular senescence and skin aging
TL;DR: The efficacy of biomarkers to detect senescence within different skin compartments and cell types, and how they may contribute to myriad manifestations of skin aging and age-related skin pathologies are discussed.
Journal ArticleDOI
The cell proliferation antigen Ki-67 organises heterochromatin
Michal Sobecki,Michal Sobecki,Karim Mrouj,Karim Mrouj,Alain Camasses,Alain Camasses,Nikolaos Parisis,Nikolaos Parisis,Emilien Nicolas,David Llères,David Llères,François Gerbe,François Gerbe,François Gerbe,Susana Prieto,Susana Prieto,Liliana Krasinska,Liliana Krasinska,Alexandre David,Alexandre David,Alexandre David,Manuel Eguren,Marie-Christine Birling,Serge Urbach,Sonia Hem,Jérôme Déjardin,Jérôme Déjardin,Marcos Malumbres,Philippe Jay,Philippe Jay,Philippe Jay,Vjekoslav Dulic,Vjekoslav Dulic,Denis L. J. Lafontaine,Robert Feil,Robert Feil,Daniel Fisher,Daniel Fisher +37 more
TL;DR: Ki-67 expression in proliferating cells spatially organises heterochromatin, thereby controlling gene expression, and is suggested to control gene expression in differentiated tissues.
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The epigenetic magic of histone lysine methylation.
TL;DR: This discovery of the first HMTase in 2000 changed my scientific career and significantly contributed to a better understanding of epigenetic control, with important implications for heterochromatin formation, X’inactivation, Polycomb group silencing and novel insights into stem cell research, nuclear reprogramming and cancer.
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Actions of human telomerase beyond telomeres.
Yu-Sheng Cong,Jerry W. Shay +1 more
TL;DR: This review will provide an update on the extracurricular activities of telomerase in apoptosis, DNA repair, stem cell function, and in the regulation of gene expression.
References
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A biomarker that identifies senescent human cells in culture and in aging skin in vivo
Goberdhan P. Dimri,X Lee,G Basile,Meileen Acosta,G Scott,C Roskelley,E E Medrano,Maarten H.K. Linskens,Ivica Rubelj,Olivia M. Pereira-Smith +9 more
TL;DR: It is shown that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture, which provides in situ evidence that senescent cells may exist and accumulate with age in vivo.
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The limited in vitro lifetime of human diploid cell strains
TL;DR: The survival curves obtained with human diploid cell strains are comparable to “multiple-hit” or “ multiple-target” curves obtain with other biological systems where an initial threshold dose is required before an exponential form of the curve is established.
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Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
TL;DR: It is shown that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest, and that the onset of cellular senescence does not simply reflect the accumulation of cell divisions, but can be prematurely activated in response to an onCogenic stimulus.
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Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.
TL;DR: It is shown that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins—a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure.
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Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.
Andrew J. Bannister,Philip Zegerman,Janet F. Partridge,Eric A. Miska,Jean O. Thomas,Robin C. Allshire,Tony Kouzarides +6 more
TL;DR: A stepwise model for the formation of a transcriptionally silent heterochromatin is provided: SUV39H1 places a ‘methyl marker’ on histone H3, which is then recognized by HP1 through its chromo domain, which may also explain the stable inheritance of theheterochromatic state.