title: A human homologue of yeast anti-silencing factor has histone chaperone activity.
abstract: BACKGROUND
  Structural changes in chromatin play essential roles in regulating eukaryotic gene expression. Silencing, potent repression of transcription in Saccharomyces cerevisiae, occurs near telomeres and at the silent mating-type loci, as well as at rDNA loci. This type of repression relates to the condensation of chromatin that occurs in the heterochromatin of multicellular organisms. Anti-silencing is a reaction by which silenced loci are de-repressed. Genetic studies revealed that several factors participate in the anti-silencing reaction. However, actions of factors and molecular mechanisms underlying anti-silencing remain unknown.
  
  
  RESULTS
  Here we report the functional activity of a highly evolutionarily conserved human factor termed CIA (CCG1-interacting factor A), whose budding yeast homologue ASF1 has anti-silencing activity. Using yeast two-hybrid screening, we isolated histone H3 as an interacting factor of CIA. We also showed that CIA binds to histones H3/H4 in vitro, and that the interacting region of histone H3 is located in the C-terminal helices. Considering the functional role of CIA as a histone-interacting protein, we found that CIA forms a nucleosome-like structure with DNA and histones.
  
  
  CONCLUSIONS
  These results show that human CIA, whose yeast homologue ASF1 is an anti-silencing factor, possesses histone chaperone activity. This leads to a better understanding of the relationship between chromatin structural changes and anti-silencing processes.
authors.affiliation: Laboratory of Developmental Biology, Institute of Molecular and Cellular Biosciences, The University of Tokyo,1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Munakata
authors.forename: N
authors.initials: N
authors.lastname: Adachi
authors.forename: N
authors.initials: N
authors.lastname: Yokoyama
authors.forename: T
authors.initials: T
authors.lastname: Kuzuhara
authors.forename: M
authors.initials: M
authors.lastname: Horikoshi
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D049770:Genes, Mating Type, Fungal; D015894:Genome, Human; D051548:Histone Acetyltransferases; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017385:Sequence Homology; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID
chemical_list: C109731:ASF1 protein, S cerevisiae; C491641:ASF1A protein, human; C491640:ASF1B protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa