Affiliation:
1. Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, New York 11794-5215
Abstract
ABSTRACT
In the yeast
Saccharomyces cerevisiae
, a and α mating-type information is stored in transcriptionally silenced cassettes called
HML
and
HMR
. Silencing of these loci, maintained by the formation of a specialized type of heterochromatin, requires
trans
-acting proteins and
cis
-acting elements. Proteins required for silencing include the Sir2 NAD
+
-dependent deacetylase, Sir3, and Sir4. Factors that bind to the
cis
elements at
HMR
and
HML
and that are important for silencing include the origin recognition complex (ORC). Mutations of any of these Sir proteins or combinations of
cis
elements result in loss of silencing.
SUM1-1
was previously identified as a dominant mutation that restores silencing to
HMR
in the absence of either the Sir proteins or some of the
cis
elements. We have investigated the novel mechanism whereby Sum1-1 causes Sir-independent silencing at
HMR
and present the following findings: Sum1-1 requires the Sir2 homolog, Hst1, for silencing and most probably requires the NAD
+
-dependent deacetylase activity of this protein. Sum1-1 interacts strongly with ORC, and this strong interaction is dependent on
HMR
DNA. Furthermore, ORC is required for Sum1-1-mediated silencing at
HMR
. These observations lead to a model for Sum1-1 silencing of
HMR
in which Sum1-1 is recruited to
HMR
by binding to ORC. Sum1-1, in turn, recruits Hst1. Hst1 then deacetylates histones or other chromatin-associated proteins to cause chromatin condensation and transcriptional silencing.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
80 articles.
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