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

Abstract

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.

Human Elongator facilitates RNA polymerase II transcription through chromatin

“…This failure suggests that the association of DSIF or Elongator with RNAPII is mutually exclusive. This is a likely possibility, as studies performed in yeast, although limited, demonstrate that not all genes are regulated by Elongator (12) and DSIF (4). Moreover, Elongator subunits, as well as Spt4, a subunit of DSIF, were found to be dispensable for viability in yeast, suggesting that more than one mechanism operates to allow efficient transcription through nucleosomes.…”

“…Relevant to the studies of Elongator function are findings demonstrating an interaction between Spt16, a subunit of FACT, and Sas3, the catalytic subunit of the NuA3 complex (9). In this regard, genetic interaction studies were performed analyzing whether GCN5, the catalytic subunit of the SAGA and the ADA complexes (25,26), interacts with ELP3 (12). Although the most relevant experiment testing for a genetic interaction between SAS3 and Elp3 was not performed, the genetic studies suggest an interaction between SAGA and Elongator (12).…”

“…In this regard, genetic interaction studies were performed analyzing whether GCN5, the catalytic subunit of the SAGA and the ADA complexes (25,26), interacts with ELP3 (12). Although the most relevant experiment testing for a genetic interaction between SAS3 and Elp3 was not performed, the genetic studies suggest an interaction between SAGA and Elongator (12). SAGA is a factor recruited to promoters by interactions with activators (27) and functions to establish transcription initiation complexes (28).…”

“…Elongator was initially found to be composed of three polypeptides (10)(11)(12). Its larger subunit is encoded by IKI3, a gene isolated earlier in a screen conferring resistance to the Kluyveromyces lactis killer toxin (13), and renamed ELP1 (10).…”

“…Importantly, ELP3 was found to encode a polypeptide possessing HAT activity with specificity to the four core histones (14). Deletion of ELP3 (or other ELP genes) confers a set of phenotypes, some of which are associated with elongation defects (10)(11)(12)14).…”