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Eukaryotic Cell, August 2004, p. 976-983, Vol. 3, No. 4
1535-9778/04/$08.00+0 DOI: 10.1128/EC.3.4.976-983.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Direct Physical and Functional Interaction of the NuA4 Complex Components Yaf9p and Swc4p
Claudia B. Bittner, Deniz T. Zeisig, Bernd B. Zeisig, and Robert K. Slany*
Department of Genetics, University Erlangen, 91058 Erlangen, Germany
Received 17 March 2004/
Accepted 13 May 2004
Saccharomyces cerevisiae Yaf9p and the mammalian leukemia-associated protein ENL share a high degree of similarity. To investigate the biological function of Yaf9p, this protein was used to search for interacting proteins in a two-hybrid system. Here, we demonstrate that Yaf9p binds directly to Swc4p, the yeast homolog of the mammalian DNA-methyltransferase-associated protein 1. Yaf9p and Swc4p associate through C-terminal domains, and both proteins coprecipitate in vitro in pull-down experiments and in vivo by immunoprecipitation. In living cells, Swc4p is present in a megadalton protein complex that shows a fractionation behavior in gel filtration similar to that of Esa1p, the histone acetyltransferase of the NuA4 complex. Recruitment of Yaf9p to DNA leads to promoter-specific transcriptional activation that can be inhibited by dominant negative Swc4p lacking the Yaf9p binding domain. Interference with Swc4p function also increases sensitivity to the microtubule toxin benomyl, a trait that corresponds to the known phenotype of a yaf9 knockout strain. In summary, the results suggest that Yaf9p and Swc4p form a protein pair that has a role in chromatin modification with possible implications also for the function of their mammalian counterparts.
* Corresponding author. Mailing address: Department of Genetics, University Erlangen, Staudtstrasse 5, 91058 Erlangen, Germany. Phone: 49 (9131) 852-8527. Fax: 49 (9131) 852-5096. E-mail:
rslany{at}biologie.uni-erlangen.de.
Eukaryotic Cell, August 2004, p. 976-983, Vol. 3, No. 4
1535-9778/04/$08.00+0 DOI: 10.1128/EC.3.4.976-983.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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