2005
DOI: 10.1016/j.devcel.2004.10.019
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Abstract: In senescent cells, specialized domains of transcriptionally silent senescence-associated heterochromatic foci (SAHF), containing heterochromatin proteins such as HP1, are thought to repress expression of proliferation-promoting genes. We have investigated the composition and mode of assembly of SAHF and its contribution to cell cycle exit. SAHF is enriched in a transcription-silencing histone H2A variant, macroH2A. As cells approach senescence, a known chromatin regulator, HIRA, enters PML nuclear bodies, whe… Show more

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Cited by 602 publications
(755 citation statements)
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“…Similarly, macroH2A1.2 is also upregulated, in contrast to control proteins, such as the canonical histone H2A. Further, the enrichment of macroH2A in SAHF is not a mere consequence of the condensed nature of SAHF chromatin, as cellular macroH2A enrichment and SAHF incorporation follow slower kinetics than the formation of DAPI-enriched heterochromatic structures (unpublished observations), confirming earlier reports (Zhang et al, 2005). This finding is supported by Western blots on human normal diploid fibroblasts IMR90, expressing hTERT and MEK:ER (ITM cells; Collado et al, 2005).…”
Section: Macroh2a Histones Are Upregulated In Senescencesupporting
confidence: 87%
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“…Similarly, macroH2A1.2 is also upregulated, in contrast to control proteins, such as the canonical histone H2A. Further, the enrichment of macroH2A in SAHF is not a mere consequence of the condensed nature of SAHF chromatin, as cellular macroH2A enrichment and SAHF incorporation follow slower kinetics than the formation of DAPI-enriched heterochromatic structures (unpublished observations), confirming earlier reports (Zhang et al, 2005). This finding is supported by Western blots on human normal diploid fibroblasts IMR90, expressing hTERT and MEK:ER (ITM cells; Collado et al, 2005).…”
Section: Macroh2a Histones Are Upregulated In Senescencesupporting
confidence: 87%
“…MacroH2A has been implicated in a permanent growth-arrest known as senescence (Pehrson and Fried, 1992;Zhang et al, 2005). This phenomenon has been described for primary cell cultures in vitro (Hayflick, 1965) and is a response to stresses like telomere shortening, accumulation of DNA damage and the overexpression of certain oncogenes (Serrano et al, 1997).…”
Section: Introductionmentioning
confidence: 99%
“…First, similar changes in chromatin structure have been described in the skin of aging baboons [41]. Second, the histone chaperone HIRA plays a key role in formation of SAHF [89][90][91][92]. As noted previously, based on immunostaining assays, this chaperone is upregulated in the dermal fibroblasts of aging baboons [40].…”
Section: Cellular Senescence Is Associated With Redistribution Of Hetsupporting
confidence: 68%
“…However, SAHF do not contain some other markers of condensed chromatin in mitotic and apoptotic cells, such as phosphoserine 10 of histone H3 (H3S10P), H2BS14P and H3S28P (45,96). SAHF are also characterized by their depletion of linker histone H1 and enrichment in at least two other proteins, namely the histone variant macroH2A and HMGA proteins (45,87,145).…”
Section: Description Of Sahfmentioning
confidence: 99%