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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
(cac
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
cac
mutants, although hir
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 cac
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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