Advanced search×

Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4.

Ryo Natsume, Masamitsu Eitoku, Yusuke Akai, Norihiko Sano, Masami Horikoshi, and Toshiya Senda

Nature 446(7133):338-41 (2007) PMID 17293877

CIA (CCG1-interacting factor A)/ASF1, which is the most conserved histone chaperone among the eukaryotes, was genetically identified as a factor for an anti-silencing function (Asf1) by yeast genetic screening. Shortly after that, the CIA-histone-H3-H4 complex was isolated from Drosophila as a histone chaperone CAF-1 stimulator. Human CIA-I/II (ASF1a/b) was identified as a histone chaperone that interacts with the bromodomain-an acetylated-histone-recognizing domain-of CCG1, in the general transcription initiation factor TFIID. Intensive studies have revealed that CIA/ASF1 mediates nucleosome assembly by forming a complex with another histone chaperone in human cells and yeast, and is involved in DNA replication, transcription, DNA repair and silencing/anti-silencing in yeast. CIA/ASF1 was shown as a major storage chaperone for soluble histones in proliferating human cells. Despite all these biochemical and biological functional analyses, the structure-function relationship of the nucleosome assembly/disassembly activity of CIA/ASF1 has remained elusive. Here we report the crystal structure, at 2.7 A resolution, of CIA-I in complex with histones H3 and H4. The structure shows the histone H3-H4 dimer's mutually exclusive interactions with another histone H3-H4 dimer and CIA-I. The carboxy-terminal beta-strand of histone H4 changes its partner from the beta-strand in histone H2A to that of CIA-I through large conformational change. In vitro functional analysis demonstrated that CIA-I has a histone H3-H4 tetramer-disrupting activity. Mutants with weak histone H3-H4 dimer binding activity showed critical functional effects on cellular processes related to transcription. The histone H3-H4 tetramer-disrupting activity of CIA/ASF1 and the crystal structure of the CIA/ASF1-histone-H3-H4 dimer complex should give insights into mechanisms of both nucleosome assembly/disassembly and nucleosome semi-conservative replication.

Referenced by 1 articles

DOI: 10.1038/nature05613
Version: za2963e q8zad q8zb9 q8zce q8zdd q8ze4 q8zf0 q8zg1

Similar articles you may find interesting…

  1. Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly.
    Yong Y Tang, Maxim V MV Poustovoitov, ... Ronen R Marmorstein

    Nat Struct Mol Biol 13(10):921-9 (2006) PMID 16980972 PMCID PMC2933817

    View PDF
  2. The FACT Spt16 "peptidase" domain is a histone H3-H4 binding module.
    Tobias Stuwe, Michael Hothorn, ... Andreas G Ladurner

    Proc Natl Acad Sci U S A 105(26):8884-9 (2008) PMID 18579787 PMCID 2449335

    We report biochemical, structural, and mutational analyses that identify the peptidase homology domain of the Schizosaccharomyces pombe FACT large subunit Spt16 (Spt16-N) as a binding module for histones H3 and H4. The 2.1-A crystal structure of Spt16-N reveals an aminopeptidase P fold whose enzymat...
    View PDF
  3. Structural basis of the nine-fold symmetry of centrioles
    Daiju D Kitagawa, Ioannis I Vakonakis, ... Michel O MO Steinmetz

    Cell 144(3):12 (2011) PMID 21277013 PMCID PMC3089914

    We demonstrate that the centriolar protein SAS-6 forms rod-shaped homodimers that interact through their N-terminal domains to form oligomers. We establish that such oligomerization is essential for centriole formation in C. elegans and human cells. We further generate a structural model of the rel...
    View PDF