Overlapping roles for the histone acetyltransferase activities of SAGA and elongator in vivo.
Elp3 and Gcn5 are histone acetyltransferases (HATs) that function in transcription as subunits of Elongator and SAGA/ADA, respectively. Here we show that mutations that impair the in vitro HAT activity of Elp3 confer typical elp phenotypes such as temperature sensitivity. Combining an elp3Delta mutation with histone H3 or H4 tail mutations confers lethality or sickness, supporting a role for Elongator in chromatin remodelling in vivo. gcn5Deltaelp3Delta double mutants display a number of severe phenotypes, and similar phenotypes result from combining the elp mutation with mutation in a gene encoding a SAGA-specific, but not an ADA-specific subunit, indicating that Elongator functionally overlaps with SAGA. Because concomitant active site alterations in Elp3 and Gcn5 are sufficient to confer severe phenotypes, the redundancy must be specifically related to the HAT activity of these complexes. In support of this conclusion, gcn5Deltaelp3Delta phenotypes are suppressed by concomitant mutation of the HDA1 and HOS2 histone deacetylases. Our results demonstrate functional redundancy among transcription-associated HAT and deacetylase activities, and indicate the importance of a fine-tuned acetylation-deacetylation balance during transcription in vivo.
Wittschieben
B O
BO
Mechanisms of Transcription Laboratory, Imperial Cancer Research Fund Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK.
Fellows
J
J
Du
W
W
Stillman
D J
DJ
Svejstrup
J Q
JQ
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000378:metabolism*; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D011494:Protein Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D002843:Chromatin; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D011494:Protein Kinases; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor