Affiliation:
1. Department of Biological Chemistry, University of California, Irvine, California, USA
Abstract
ABSTRACT
CAF-1 and HIR are highly conserved histone chaperone protein complexes that function in the assembly of nucleosomes onto chromatin. CAF-1 is characterized as having replication-coupled nucleosome activity, whereas the HIR complex can assemble nucleosomes independent of replication. Histone H3K56 acetylation, controlled by the acetyltransferase Rtt109 and deacetylase Hst3, also plays a significant role in nucleosome assembly. In this study, we generated a set of deletion mutants to genetically characterize pathway-specific and overlapping functions of CAF-1 and HIR in
C. albicans
. Their roles in epigenetic maintenance of cell type were examined by using the white-opaque switching system in
C. albicans
. We show that CAF-1 and HIR play conserved roles in UV radiation recovery, repression of histone gene expression, correct chromosome segregation, and stress responses. Unique to
C. albicans
, the
cac2Δ/Δ
mutant shows increased sensitivity to the Hst3 inhibitor nicotinamide, while the
rtt109Δ/Δ cac2Δ/Δ
and
hir1Δ/Δ cac2Δ/Δ
mutants are resistant to nicotinamide. CAF-1 plays a major role in maintaining cell types, as the
cac2Δ/Δ
mutant exhibited increased switching frequencies in both directions and switched at a high frequency to opaque in response to nicotinamide. Like the
rtt109Δ/Δ
mutant, the
hir1Δ/Δ cac2Δ/Δ
double mutant is defective in maintaining the opaque cell fate and blocks nicotinamide-induced opaque formation, and the defects are suppressed by ectopic expression of the master white-opaque regulator Wor1. Our data suggest an overlapping function of CAF-1 and HIR in epigenetic regulation of cell fate determination in an H3K56 acetylation-associated manner.
Publisher
American Society for Microbiology
Subject
Molecular Biology,General Medicine,Microbiology
Cited by
26 articles.
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