Structure of the yeast histone H3-ASF1 interaction: implications for chaperone mechanism, species-specific interactions, and epigenetics

BMC Struct Biol. 2006 Dec 13;6:26. doi: 10.1186/1472-6807-6-26.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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

Substances

  • ASF1A protein, human
  • Cell Cycle Proteins
  • Molecular Chaperones
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae

Associated data

  • PDB/2IDC