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.

Histone chaperones in nucleosome eviction and histone exchange

“…These structures have been very rewarding in that they provide intriguing insights into the mechanism of nucleosome disassembly. In vitro and in vivo evidence that Asf1 binds a heterodimer of H3/H4 (and not, as previously assumed, a (H3-H4) 2 tetramer) [51] [52] [53] were confirmed by x-ray crystallography, and the structural basis for these observations became immediately obvious. Asf1 binds the C-terminal α3-helix of H3, preventing the formation of the (H3-H4) 2 through the four-helix bundle (Figure 4).…”

Histone chaperone ASF1 cooperates with the Brahma chromatin-remodelling machinery

“…First, mutation of the yeast asf1 gene results in the suppression of S-phase-specific histone genes activation (Sutton et al 2001). Second, it was shown that ASF1 interacts with bromodomain-containing subunits of TFIID (Munakata et al 2000;Chimura et al 2002).…”

“…Nucleosome assembly is the process by which newly synthesized histones are loaded onto naked DNA. This function is performed primarily by histone chaperones like Chromatin Assembly Factor-1 (CAF-1) and Nucleosome Assembly Protein-1 (NAP-1; Munakata et al 2000;Philpott et al 2000;Mello and Almouzni 2001). However, nucleosome assembly factors alone are unable to efficiently produce long and regularly spaced nucleosomal arrays.…”

“…Both biochemical and genetic studies have shown that ASF1 acts as a histone chaperone (Tyler et al , 2001Munakata et al 2000), which in concert with another histone chaperone, CAF-1, is thought to deposit histones H3 and H4 tetramers onto naked DNA. The assembly of nucleosome particles is completed by the addition of two dimers of histones H2A and H2B, probably by the histone chaperone, NAP-1 (Luger et al 1997;Philpott et al 2000;Mello and Almouzni 2001).…”

The Histone Chaperone Facilitates Chromatin Transcription (FACT) Protein Maintains Normal Replication Fork Rates

“…Another evolutionarily conserved histone chaperone is CCG1-interacting factor A (CIA) (19), whose budding yeast homologue, anti-silencing function 1 (Asf1), has been shown to possess anti-silencing activity (20), also participates in the nucleosome reassembly reaction on the daughter DNA strands (21). Recently, CIA/Asf1 has been reported to regulate replication fork progression and histone supply and demand in the DNA replication process (22,23).…”