Molecular and Cellular Biology, May 2001, p. 3514-3522, Vol. 21, No. 10
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.10.3514-3522.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
andDepartment of Biochemistry and Cell Biology, State University of New York, Stony Brook, New York 11794-5215
Received 20 November 2000/Returned for modification 3 January 2001/Accepted 15 February 2001
In the yeast Saccharomyces cerevisiae, a and
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.
Permanent address: Institute of Biochemistry and Biophysics, Polish
Academy of Sciences, 02-106 Warsaw, Poland.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|