The Schizosaccharomyces pombe HIRA-like protein Hip1 is required for the periodic expression of histone genes and contributes to the function of complex centromeres.

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 slm9 Delta 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.

The forkhead transcription factor Fkh2 regulates the cell division cycle of Schizosaccharomyces pombe.

In eukaryotes the regulation of gene expression plays a key role in controlling cell cycle progression. Here, we demonstrate that a forkhead transcription factor, Fkh2, regulates the periodic expression of cdc15(+) and spo12(+) in the M and G(1) phases of the cell division cycle in the fission yeast Schizosaccharomyces pombe. We also show that Fkh2 is important for several cell cycle processes, including cell morphology and cell separation, nuclear structure and migration, and mitotic spindle function. We find that the expression of fkh2(+) is itself regulated in a cell cycle-dependent manner in G(1) coincident with the expression of cdc18(+), a Cdc10-regulated gene. However, fkh2(+) expression is independent of Cdc10 function. Fkh2 was found to be phosphorylated during the cell division cycle, with a timing that suggests that this posttranslational modification is important for cdc15(+) and spo12(+) expression. Related forkhead proteins regulate G(2) and M phase-specific gene expression in the evolutionarily distant Saccharomyces cerevisiae, suggesting that these proteins play conserved roles in regulating cell cycle processes in eukaryotes.