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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.

A Novel Form of Transcriptional Silencing by Sum1-1 Requires Hst1 and the Origin Recognition Complex

Ann Sutton, Ryan C. Heller, Joseph Landry, Jennifer S. Choy, Agnieszka Sirko,dagger and Rolf Sternglanz*

Department 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 alpha  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.


* Corresponding author. Mailing address: Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY 11794-5215. Phone: (631) 632-8565. Fax: (631) 632-8575. E-mail: rolf{at}life.bio.sunysb.edu.

dagger Permanent address: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland.


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.



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