A human homologue of yeast anti-silencing factor has histone chaperone activity

Background: Structural changes in chromatin play essential roles in regulat ing eukaryotic gene expression. Silencing, potent repression of transcripti on in Saccharomyces cerevisiae, occurs near telomeres and at the silent mat ing-type loci, as well as at rDNA loci. This type of repression relates to the condensation of chromatin that occurs in the heterochromatin of multice llular organisms. Anti-silencing is a reaction by which silenced loci are d e-repressed. Genetic studies revealed that several factors participate in t he anti-silencing reaction. However, actions of factors and molecular mecha nisms 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 buddin g 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 lea ds to a better understanding of the relationship between chromatin structur al changes and anti-silencing processes.