Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA
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Publisher version
UMass Chan Affiliations
Program in Gene Function and ExpressionDocument Type
ArticlePublication Date
2005-01-29Keywords
Amino Acid SequenceBlotting, Western
Cell Aging
Cell Count
Cell Cycle
Cell Cycle Proteins
Cell Line
Chromosomal Proteins, Non-Histone
Dosage Compensation, Genetic
Gene Expression RegulationHeterochromatinHistonesImmunohistochemistryImmunoprecipitationIndolesNeoplasm ProteinsNuclear ProteinsRecombinant Fusion ProteinsRepressor ProteinsTime FactorsTranscription FactorsTransfectionTumor Suppressor Proteinsras ProteinsGenetics and Genomics
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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, where it transiently colocalizes with HP1 proteins, prior to incorporation of HP1 proteins into SAHF. A physical complex containing HIRA and another chromatin regulator, ASF1a, is rate limiting for formation of SAHF and onset of senescence, and ASF1a is required for formation of SAHF and efficient senescence-associated cell cycle exit. These data indicate 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.Source
Dev Cell. 2005 Jan;8(1):19-30. Link to article on publisher's siteDOI
10.1016/j.devcel.2004.10.019Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43923PubMed ID
15621527Related Resources
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