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dc.contributor.authorAntczak, Andrew J.
dc.contributor.authorTsubota, Toshiaki
dc.contributor.authorKaufman, Paul D.
dc.contributor.authorBerger, James M.
dc.date2022-08-11T08:10:15.000
dc.date.accessioned2022-08-23T17:00:57Z
dc.date.available2022-08-23T17:00:57Z
dc.date.issued2006-12-15
dc.date.submitted2011-04-19
dc.identifier.citationBMC Struct Biol. 2006 Dec 13;6:26. <a href="http://dx.doi.org/10.1186/1472-6807-6-26">Link to article on publisher's site</a>
dc.identifier.issn1472-6807 (Linking)
dc.identifier.doi10.1186/1472-6807-6-26
dc.identifier.pmid17166288
dc.identifier.urihttp://hdl.handle.net/20.500.14038/43903
dc.description.abstractBACKGROUND: The histone H3/H4 chaperone Asf1 (anti-silencing function 1) is required for the establishment and maintenance of proper chromatin structure, as well as for genome stability in eukaryotes. Asf1 participates in both DNA replication-coupled (RC) and replication-independent (RI) histone deposition reactions in vitro and interacts with complexes responsible for both pathways in vivo. Asf1 is known to directly bind histone H3, however, high-resolution structural information about the geometry of this interaction was previously unknown. RESULTS: Here we report the structure of a histone/histone chaperone interaction. We have solved the 2.2 A crystal structure of the conserved N-terminal immunoglobulin fold domain of yeast Asf1 (residues 2-155) bound to the C-terminal helix of yeast histone H3 (residues 121-134). The structure defines a histone-binding patch on Asf1 consisting of both conserved and yeast-specific residues; mutation of these residues abrogates H3/H4 binding affinity. The geometry of the interaction indicates that Asf1 binds to histones H3/H4 in a manner that likely blocks sterically the H3/H3 interface of the nucleosomal four-helix bundle. CONCLUSION: These data clarify how Asf1 regulates histone stoichiometry to modulate epigenetic inheritance. The structure further suggests a physical model in which Asf1 contributes to interpretation of a "histone H3 barcode" for sorting H3 isoforms into different deposition pathways.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17166288&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectAnimals
dc.subjectCell Cycle Proteins
dc.subjectDimerization
dc.subject*Epigenesis, Genetic
dc.subjectGene Silencing
dc.subjectHumans
dc.subjectMolecular Chaperones
dc.subjectProtein Binding
dc.subjectSaccharomyces cerevisiae
dc.subjectSilent Information Regulator Proteins, Saccharomyces
dc.subjectcerevisiae
dc.subjectSpecies Specificity
dc.subjectGenetics and Genomics
dc.titleStructure of the yeast histone H3-ASF1 interaction: implications for chaperone mechanism, species-specific interactions, and epigenetics
dc.typeJournal Article
dc.source.journaltitleBMC structural biology
dc.source.volume6
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1114&amp;context=pgfe_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/pgfe_pp/114
dc.identifier.contextkey1946769
refterms.dateFOA2022-08-23T17:00:57Z
html.description.abstract<p>BACKGROUND: The histone H3/H4 chaperone Asf1 (anti-silencing function 1) is required for the establishment and maintenance of proper chromatin structure, as well as for genome stability in eukaryotes. Asf1 participates in both DNA replication-coupled (RC) and replication-independent (RI) histone deposition reactions in vitro and interacts with complexes responsible for both pathways in vivo. Asf1 is known to directly bind histone H3, however, high-resolution structural information about the geometry of this interaction was previously unknown. RESULTS: Here we report the structure of a histone/histone chaperone interaction. We have solved the 2.2 A crystal structure of the conserved N-terminal immunoglobulin fold domain of yeast Asf1 (residues 2-155) bound to the C-terminal helix of yeast histone H3 (residues 121-134). The structure defines a histone-binding patch on Asf1 consisting of both conserved and yeast-specific residues; mutation of these residues abrogates H3/H4 binding affinity. The geometry of the interaction indicates that Asf1 binds to histones H3/H4 in a manner that likely blocks sterically the H3/H3 interface of the nucleosomal four-helix bundle. CONCLUSION: These data clarify how Asf1 regulates histone stoichiometry to modulate epigenetic inheritance. The structure further suggests a physical model in which Asf1 contributes to interpretation of a "histone H3 barcode" for sorting H3 isoforms into different deposition pathways.</p>
dc.identifier.submissionpathpgfe_pp/114
dc.contributor.departmentProgram in Gene Function and Expression
dc.source.pages26


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