TY - JOUR

T1 - Overlapping roles for the histone acetyltransferase activities of SAGA and Elongator in vivo

AU - Wittschieben, Birgitte

AU - Fellows, Jane

AU - Wendy, Du

AU - Stillman, David J.

AU - Svejstrup, Jesper Q.

PY - 2000/6/15

Y1 - 2000/6/15

N2 - 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 elp3Δ mutation with histone H3 or H4 tail mutations confers lethality or sickness, supporting a role for Elongator in chromatin remodelling in vivo. gcn5Δelp3Δ 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, gcn5Δelp3Δ 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.

AB - 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 elp3Δ mutation with histone H3 or H4 tail mutations confers lethality or sickness, supporting a role for Elongator in chromatin remodelling in vivo. gcn5Δelp3Δ 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, gcn5Δelp3Δ 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.

KW - Elongator

KW - ELP3

KW - GCN5

KW - Histone acetyltransferase

KW - Histone deacetylase

UR - http://www.scopus.com/inward/record.url?scp=0034660330&partnerID=8YFLogxK

U2 - 10.1093/emboj/19.12.3060

DO - 10.1093/emboj/19.12.3060

M3 - Journal article

C2 - 10856249

AN - SCOPUS:0034660330

VL - 19

SP - 3060

EP - 3068

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

IS - 12

ER -