Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA
Poustovoitov, Maxim V.
Santos, Hidelita A.
Daganzo, Sally M.
Erzberger, Jan P.
Serebriiskii, Ilya G.
Canutescu, Adrian A.
Dunbrack, Roland L.
Pehrson, John R.
Berger, James M.
Kaufman, Paul D.
Adams, Peter D.
UMass Chan AffiliationsProgram in Gene Function and Expression
Document TypeJournal Article
KeywordsAmino Acid Sequence
Cell Cycle Proteins
Chromosomal Proteins, Non-Histone
Dosage Compensation, Genetic
Gene Expression Regulation
Recombinant Fusion Proteins
Tumor Suppressor Proteins
Genetics and Genomics
MetadataShow full item record
AbstractIn 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.
SourceDev Cell. 2005 Jan;8(1):19-30. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/43923
Related ResourcesLink to Article in PubMed
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