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Mol Cell Biol, August 1998, p. 4793-4806, Vol. 18, No. 8
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Hir Proteins Are Required for Position-Dependent Gene Silencing in Saccharomyces cerevisiae in the Absence of Chromatin Assembly Factor I

Paul D. Kaufman,1 * Jennifer L. Cohen,1 and Mary Ann Osley2

Lawrence Berkeley National Laboratory and Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3206,1 and Program in Molecular Biology, Sloan Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, New York, New York, 100212

Received 11 March 1998/Returned for modification 15 April 1998/Accepted 14 May 1998

Chromatin assembly factor I (CAF-I) is a three-subunit histone-binding complex conserved from the yeast Saccharomyces cerevisiae to humans. Yeast cells lacking CAF-I (cacDelta mutants) have defects in heterochromatic gene silencing. In this study, we showed that deletion of HIR genes, which regulate histone gene expression, synergistically reduced gene silencing at telomeres and at the HM loci in cacDelta mutants, although hirDelta mutants had no silencing defects when CAF-I was intact. Therefore, Hir proteins are required for an alternative silencing pathway that becomes important in the absence of CAF-I. Because Hir proteins regulate expression of histone genes, we tested the effects of histone gene deletion and overexpression on telomeric silencing and found that alterations in histone H3 and H4 levels or in core histone stoichiometry reduced silencing in cacDelta mutants but not in wild-type cells. We therefore propose that Hir proteins contribute to silencing indirectly via regulation of histone synthesis. However, deletion of combinations of CAC and HIR genes also affected the growth rate and in some cases caused partial temperature sensitivity, suggesting that global aspects of chromosome function may be affected by the loss of members of both gene families.

* Corresponding author. Mailing address: 351 Donner Laboratory, Lawrence Berkeley National Laboratory, Berkeley, CA 94720-3206. Phone: (510) 486-5846. Fax: (510) 486-6488. E-mail: pdkaufman{at}lbl.gov.

Mol Cell Biol, August 1998, p. 4793-4806, Vol. 18, No. 8
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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