UMMS Affiliation

Program in Gene Function and Expression

Date

12-15-2006

Document Type

Article

Medical Subject Headings

Animals; Cell Cycle Proteins; Dimerization; *Epigenesis, Genetic; Gene Silencing; Humans; Molecular Chaperones; Protein Binding; Saccharomyces cerevisiae; Silent Information Regulator Proteins, Saccharomyces; cerevisiae; Species Specificity

Disciplines

Genetics and Genomics

Abstract

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.

Rights and Permissions

Citation: BMC Struct Biol. 2006 Dec 13;6:26. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

17166288

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