Acetylation of Rsc4p by Gcn5p is essential in the absence of histone H3 acetylation.
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.
Choi
Jennifer K
JK
Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Grimes
Daniel E
DE
Rowe
Keegan M
KM
Howe
Leann J
LJ
D000107:Acetylation; D019943:Amino Acid Substitution; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D050296:Microbial Viability; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C103337:RSC complex, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor