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
Citations
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The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression
TL;DR: This review focuses on the cell-cycle arrest and apoptosis functions of p53, their roles in tumor suppression, and the regulation of cell fate decision after p53 activation.
Journal ArticleDOI
Lamin B1 loss is a senescence-associated biomarker
Adam Freund,Adam Freund,Adam Freund,Remi-Martin Laberge,Marco Demaria,Judith Campisi,Judith Campisi +6 more
TL;DR: This study rigorously defines lamin B1 loss as a marker of senescence in response to all classic signals ofsenescence, including DNA damage, oncogene activation, and replicative exhaustion.
Journal ArticleDOI
The profile of repeat‐associated histone lysine methylation states in the mouse epigenome
Joost H.A. Martens,Roderick J. O'Sullivan,Ulrich Braunschweig,Susanne Opravil,Martin Radolf,Peter Steinlein,Thomas Jenuwein +6 more
TL;DR: A profile of repressive histone lysine methylation states for the repetitive complement of four distinct mouse epigenomes is defined and tandem repeats and dsRNA are suggested as primary triggers for more stable chromatin imprints.
Journal ArticleDOI
Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells
Bogdan Bintu,Leslie J. Mateo,Jun-Han Su,Nicholas A Sinnott-Armstrong,Mirae Parker,Seon Kinrot,Kei Yamaya,Alistair N. Boettiger,Xiaowei Zhuang +8 more
TL;DR: A super-resolution chromatin tracing method that allows determination of both the structural features and their genomic coordinates with high resolution in single cells is reported, suggesting that cohesin is not required for the formation or maintenance of single-cell domain structures, but that their preferential boundary positions are influenced by cohes in-CTCF interaction.
Journal ArticleDOI
Formation of MacroH2A-Containing Senescence-Associated Heterochromatin Foci and Senescence Driven by ASF1a and HIRA
Rugang Zhang,Maxim Poustovoitov,Maxim Poustovoitov,Xiaofen Ye,Hidelita Santos,Wei Chen,Sally M. Daganzo,Sally M. Daganzo,Jan P. Erzberger,Ilya G. Serebriiskii,Adrian A. Canutescu,Roland L. Dunbrack,John R. Pehrson,James M. Berger,Paul D. Kaufman,Paul D. Kaufman,Peter D. Adams +16 more
TL;DR: Analysis of composition and mode of assembly of SAHF indicates that HIRA and ASF1a drive formation of macroH2A-containing SAHF and senescence-associated cell cycle exit, via a pathway that appears to depend on flux of heterochromatic proteins through PML bodies.
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.
Journal ArticleDOI
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.