A human homologue of yeast anti-silencing factor has histone chaperone activity.
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.
Munakata
T
T
Laboratory of Developmental Biology, Institute of Molecular and Cellular Biosciences, The University of Tokyo,1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Adachi
N
N
Yokoyama
N
N
Kuzuhara
T
T
Horikoshi
M
M
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
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