This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.00164-08v1 28/14/4445    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Biswas, D. Articles by Stillman, D. J. PubMed PubMed Citation Articles by Biswas, D. Articles by Stillman, D. J.

Next Article 

Molecular and Cellular Biology, July 2008, p. 4445-4458, Vol. 28, No. 14
0270-7306/08/$08.00+0     doi:10.1128/MCB.00164-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Different Genetic Functions for the Rpd3(L) and Rpd3(S) Complexes Suggest Competition between NuA4 and Rpd3(S)

Debabrata Biswas ,^, Shinya Takahata, and David J. Stillman^*

Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84112

Received 1 February 2008/ Returned for modification 29 February 2008/ Accepted 8 May 2008

Rpd3(L) and Rpd3(S) are distinct multisubunit complexes containing the Rpd3 histone deacetylase. Disruption of the GCN5 histone acetyltransferase gene shows a strong synthetic phenotype when combined with either an sds3 mutation affecting only the Rpd3(L) complex or an rco1 mutation affecting only Rpd3(S). However, these synthetic growth defects are not seen in a gcn5 sds3 rco1 triple mutant, suggesting that the balance between Rpd3(L) and Rpd3(S) is critical in cells lacking Gcn5. Different genetic interactions are seen with mutations affecting the FACT chromatin reorganizing complex. An sds3 mutation affecting only Rpd3(L) has a synthetic defect with FACT mutants, while rco1 and eaf3 mutations affecting Rpd3(S) suppress FACT mutant phenotypes. Rpd3(L) therefore acts in concert with FACT, but Rpd3(S) opposes it. Combining FACT mutations with mutations in the Esa1 subunit of the NuA4 histone acetyltransferase results in synthetic growth defects, and these can be suppressed by an rco1 or set2 mutation. An rco1 mutation suppresses phenotypes caused by mutations in the ESA1 and ARP4 subunits of NuA4, while Rco1 overexpression exacerbates these defects. These results suggest a model in which NuA4 and Rpd3(S) compete. Chromatin immunoprecipitation experiments show that eliminating Rpd3(S) increases the amount of NuA4 binding to the ARG3 promoter during transcriptional activation and to the sites of DNA repair induced by a double-strand break. Our results suggest that the Rpd3(L) and Rpd3(S) complexes have distinct functions in vivo and that the relative amounts of the two forms alter the effectiveness of other chromatin-altering complexes, such as FACT and NuA4.

Published ahead of print on 19 May 2008.

These authors contributed equally to this work.

Present address: Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, NY 10065.