The Schizosaccharomyces pombe HIRA-Like Protein Hip1 Is Required for the Periodic Expression of Histone Genes and Contributes to the Function of Complex Centromeres

Newcastle University, Newcastle-on-Tyne, England, United Kingdom
Molecular and Cellular Biology (Impact Factor: 4.78). 06/2004; 24(10):4309-20. DOI: 10.1128/MCB.24.10.4309-4320.2004
Source: PubMed


HIRA-like (Hir) proteins are evolutionarily conserved and are implicated in the assembly of repressive chromatin. In Saccharomyces cerevisiae, Hir proteins contribute to the function of centromeres. However, S. cerevisiae has point centromeres that are structurally different from the complex centromeres of metazoans. In contrast, Schizosaccharomyces pombe has complex centromeres whose domain structure is conserved with that of human centromeres. Therefore, we examined the functions
of the fission yeast Hir proteins Slm9 and the previously uncharacterised protein Hip1. Deletion of hip1+ resulted in phenotypes that were similar to those described previously for slm9Δ cells: a cell cycle delay, synthetic lethality with cdc25-22, and poor recovery from nitrogen starvation. However, while it has previously been shown that Slm9 is not required for the
periodic expression of histone H2A, we found that loss of Hip1 led to derepression of core histone genes expression outside
of S phase. Importantly, we found that deletion of either hip1+ or slm9+ resulted in increased rates of chromosome loss, increased sensitivity to spindle damage, and reduced transcriptional silencing
in the outer centromeric repeats. Thus, S. pombe Hir proteins contribute to pericentromeric heterochromatin, and our data thus suggest that Hir proteins may be required for
the function of metazoan centromeres.

  • Source
    • "Clr6 protein resides in two complexes, and attenuation of activity of either complex leads to defective TGS at centromeres and other heterochromatic loci (Nicolas et al. 2007). Clr6 can associate with a histone H3 and H4 chaperone complex containing Asf1 and HIRA, and the combined effect of these proteins is to promote nucleosomal occupancy and histone deacetylation to allow assembly of repressive chromatin (Blackwell et al. 2004; Yamane et al. 2011). Loss of Sir2 correlates with an increase in H3K9Ac, which is refractory to the activity of Clr4 in H3K9 methylation, and results in some attenuation of centromeric heterochromatin (Shankaranarayana et al. 2003). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Distinct regions of the eukaryotic genome are packaged into different types of chromatin, with euchromatin representing gene rich, transcriptionally active regions and heterochromatin more condensed and gene poor. The assembly and maintenance of heterochromatin is important for many aspects of genome control, including silencing of gene transcription, suppression of recombination, and to ensure proper chromosome segregation. The precise mechanisms underlying heterochromatin establishment and maintenance are still unclear, but much progress has been made towards understanding this process during the last few years, particularly from studies performed in fission yeast. In this review, we hope to provide a conceptual model of centromeric heterochromatin in fission yeast that integrates our current understanding of the competing forces of transcription, replication, and RNA decay that influence its assembly and propagation.
    Full-text · Article · Jun 2012 · Chromosome Research
  • Source
    • "The HIR complex functions in several chromatin-related processes including chromatin assembly (Sharp et al. 2001; Green et al. 2005; Prochasson et al. 2005), kinetochore function (Sharp et al. 2002), and transcription elongation (Formosa et al. 2002; Nourani et al. 2006). HIRA, the human homolog of yeast Hir1 and Hir2 (Hall et al. 2001), is also a histone chaperone (Ray-Gallet et al. 2002), and Hira of S. pombe is required for both heterochromatin formation and repression of antisense transcription (Blackwell et al. 2004; Anderson et al. 2009; Yamane et al. 2011). The CAF-1 complex was originally identified from Hela cells as an activity that assembles nucleosomes onto replicating DNA (Stillman 1986; Smith and Stillman 1989). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Understanding the mechanisms by which chromatin structure controls eukaryotic transcription has been an intense area of investigation for the past 25 years. Many of the key discoveries that created the foundation for this field came from studies of Saccharomyces cerevisiae, including the discovery of the role of chromatin in transcriptional silencing, as well as the discovery of chromatin-remodeling factors and histone modification activities. Since that time, studies in yeast have continued to contribute in leading ways. This review article summarizes the large body of yeast studies in this field.
    Full-text · Article · Feb 2012 · Genetics
  • Source
    • "The importance of the HIR complex is seen by its evolutionary conservation , as it is found in several species, including yeasts, Arabidopsis, Drosophila, Xenopus, chicken, fish, mice and humans [25] [26] [27] [28] [29] [30] [31] [32]. In the fission yeast S. pombe, the HIRA complex is composed of Hip1, Slm9, Hip3 and Hip4 which are homologues of Hir1, Hir2, Hir3 and Hpc2, respectively [33] [34] [35]. The human HIRA protein is the homologue of Hir1 and Hir2 and is required for histone H3.3 deposition at active genes independently of DNA replication [25,36–38]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The HIR complex, which is comprised of the four proteins Hir1, Hir2, Hir3 and Hpc2, was first characterized as a repressor of three of the four histone gene loci in Saccharomyces cerevisiae. Using a bioinformatical approach, previous studies have identified a region of Hpc2 that is conserved in Schizosaccharomyces pombe and humans. Using a similar approach, we identified two additional domains, CDI and CDII, of the Hpc2 protein that are conserved among yeast species related to S. cerevisiae. We showed that the N terminal CDI domain (spanning amino acids 63-79) is dispensable for HIR complex assembly, but plays an essential role in the repression of the histone genes by recruiting the HIR complex to the HIR-dependent histone gene loci. The second conserved domain, CDII (spanning amino acids 452-480), is required for the stability of the Hpc2 protein itself as well as for the assembly of the HIR complex. In addition, we report a novel separation-of-function mutation within CDI of Hpc2, which causes derepression of the histone genes but does not confer other reported hir/hpc- phenotypes (such as Spt phenotypes, heterochromatin silencing defects and repression of cryptic promoters). This is the first direct demonstration that a separation-of-function mutation exists within the HIR complex.
    Full-text · Article · Jul 2011 · Biochimica et Biophysica Acta
Show more