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Molecular and Cellular Biology, December 2008, p. 6967-6972, Vol. 28, No. 23
0270-7306/08/$08.00+0     doi:10.1128/MCB.00570-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Acetylation of Rsc4p by Gcn5p Is Essential in the Absence of Histone H3 Acetylation {triangledown}

Jennifer K. Choi, Daniel E. Grimes, Keegan M. Rowe, and LeAnn J. Howe*

Department of Biochemistry and Molecular Biology and Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, Vancouver V6T 1Z3, British Columbia, Canada

Received 8 April 2008/ Returned for modification 10 June 2008/ Accepted 12 September 2008

Rsc4p, a subunit of the RSC chromatin-remodeling complex, is acetylated at lysine 25 by Gcn5p, a well-characterized histone acetyltransferase (HAT). Mutation of lysine 25 does not result in a significant growth defect, and therefore whether this modification is important for the function of the essential RSC complex was unknown. In a search to uncover the molecular basis for the lethality resulting from loss of multiple histone H3-specific HATs, we determined that loss of Rsc4p acetylation is lethal in strains lacking histone H3 acetylation. Phenotype comparison of mutants with arginine and glutamine substitutions of acetylatable lysines within the histone H3 tail suggests that it is a failure to neutralize the charge of the H3 tail that is lethal in strains lacking Rsc4p acetylation. We also demonstrate that Rsc4p acetylation does not require any of the known Gcn5p-dependent HAT complexes and thus represents a truly novel function for Gcn5p. These results demonstrate for the first time the vital and yet redundant functions of histone H3 and Rsc4p acetylation in maintaining cell viability.


* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada. Phone: (604) 822-6297. Fax: (604) 822-5227. E-mail: ljhowe{at}interchange.ubc.ca

{triangledown} Published ahead of print on 22 September 2008.


Molecular and Cellular Biology, December 2008, p. 6967-6972, Vol. 28, No. 23
0270-7306/08/$08.00+0     doi:10.1128/MCB.00570-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.