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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ING2 Regulates the Onset of Replicative Senescence by Induction of p300-Dependent p53 Acetylation
Rémy Pedeux,Sagar Sengupta,Jiang Cheng Shen,Oleg N. Demidov,Shin'ichi Saito,Hitoshi Onogi,Kensuke Kumamoto,Stephen Wincovitch,Susan H. Garfield,Mary G. McMenamin,Makoto Nagashima,Steven R. Grossman,Ettore Appella,Curtis C. Harris +13 more
TL;DR: IT is demonstrated that ING2 can act as a cofactor of p300 for p53 acetylation and thereby plays a positive regulatory role during p53-mediated replicative senescence.
Journal ArticleDOI
Sumoylation at chromatin governs coordinated repression of a transcriptional program essential for cell growth and proliferation.
Hélène Neyret-Kahn,Hélène Neyret-Kahn,Moussa Benhamed,Moussa Benhamed,Tao Ye,Stéphanie Le Gras,Jack-Christophe Cossec,Jack-Christophe Cossec,Pierre Lapaquette,Pierre Lapaquette,Oliver Bischof,Oliver Bischof,Maia Ouspenskaia,Mary Dasso,Jacob S. Seeler,Jacob S. Seeler,Irwin Davidson,Anne Dejean,Anne Dejean +18 more
TL;DR: The genome-wide localization of SUMO1 and SUMO2/3, as well as of UBC9 and PIASY, two markers for active sumoylation, along with Pol II and histone marks in proliferating versus senescent human fibroblasts are determined to suggest that maintenance of a repressive environment at histone and tRNA loci is a hallmark of the senescent state.
Journal ArticleDOI
Pluripotent stem cells escape from senescence-associated DNA methylation changes
Carmen M. Koch,Kristina Reck,Kaifeng Shao,Qiong Lin,Sylvia Joussen,Patrick Ziegler,Gudrun Walenda,Wolf Drescher,Bertram Opalka,Tobias May,Tim H. Brümmendorf,Martin Zenke,Tomo Saric,Wolfgang Wagner +13 more
TL;DR: The results indicate that long-term culture is associated with an epigenetically controlled process that stalls cells in a particular functional state, whereas irradiation-induced senescence and immortalization are not causally related to this process.
Journal ArticleDOI
p16(INK4a) prevents centrosome dysfunction and genomic instability in primary cells.
Kimberly M. McDermott,Jianmin Zhang,Jianmin Zhang,Charles R. Holst,Charles R. Holst,B. Krystyna Kozakiewicz,Veena Singla,Thea D. Tlsty +7 more
TL;DR: Demonstration of centrosome dysfunction in cells due to loss of p16INK4a suggests that, under the appropriate conditions, these cells can become aneuploid, which may provide the necessary proproliferation and antiapoptotic mechanisms needed for the earliest stages of tumorigenesis.
Journal ArticleDOI
Inflammatory signaling and cellular senescence
TL;DR: The dual roles of the inflammatory cytokines produced by senescent cells in the pathogenesis of cancer, and the signaling pathway mediating their role in cellular senescence are discussed.
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.