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Molecular and Cellular Biology, May 2004, p. 4309-4320, Vol. 24, No. 10
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.10.4309-4320.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Chris Blackwell,1,{dagger} Kate A. Martin,1,{dagger} Amanda Greenall,1 Alison Pidoux,2 Robin C. Allshire,2 and Simon K. Whitehall1*

Cell and Molecular Biosciences, University of Newcastle upon Tyne, Newcastle NE2 4HH,1 Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom2

Received 4 November 2003/ Returned for modification 1 December 2003/ Accepted 23 February 2004

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.

* Corresponding author. Mailing address: Cell and Molecular Biosciences, University of Newcastle upon Tyne, Newcastle NE2 4HH, United Kingdom. Phone: 44 (0)191 222 5989. Fax: 44 (0)191 222 7424. E-mail: S.K.Whitehall{at}ncl.ac.uk.

{dagger} C.B. and K.A.M. contributed equally to this study.

Molecular and Cellular Biology, May 2004, p. 4309-4320, Vol. 24, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.10.4309-4320.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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