Multi-tasking on chromatin with the SAGA coactivator complexes

Abstract

Over the past 10 years, much progress has been made to understand the roles of the similar, yet distinct yeast SAGA and SLIK coactivator complexes involved in histone post-translational modification and gene regulation. Many different groups have elucidated functions of the SAGA complexes including identification of novel components, which have conferred additional distinct functions. Together, recent studies demonstrate unique attributes of the SAGA coactivator complexes in histone acetylation, methylation, phosphorylation, and deubiquitination. In addition to roles in transcriptional activation with the 19S proteasome regulatory particle, recent evidence also suggests functions for SAGA in elongation and mRNA export. The modular nature of SAGA allows this approximately 1.8 MDa complex to organize its functions and carry out multiple roles during transcription, particularly under conditions of cellular stress.

Figure 1

Composition of the SAGA family of HAT/coactivator complexes. Shown is a representation of the reported subunits of the SAGA and SLIK complexes and homologues in the mammalian SAGA family of complexes PCAF, STAGA and TFTC. Proteins are grouped according to their designation as histone acetyltransferase (HAT), TAF, Spt, Ada, Ataxin-7, Tra1 (ATM-like), Chd1 or proteins involved in histone H2B deubiquitination (H2B deUb). The yeast Spt8 and Rtg2 proteins are unique to the SAGA and SLIK complexes respectively. Shaded horizontal bars represent those yeast proteins with homologues identified in one or more of the mammalian complexes. Additional TFTC and STAGA associated proteins, such as SAP130 and DDB1, are not shown.

Figure 2

Multi-tasking on chromatin with the SAGA coactivator complexes. SAGA and SLIK subunits are organized into modules that carry out distinct functions. Shown is a representation of SAGA recruited to a promoter functioning in transcriptional activation. Tra1 associates with DNA-binding transcription factor/activator (TF) proteins and this interaction is strengthened by the 19S proteasome regulatory particle (RP). Set1-mediated H3-K4 methylation and Snf1-mediated H3-S10 phosphorylation promote the HAT activity of Gcn5. The bromo- and chromodomains within SAGA mediate additional chromatin interaction through association with modified histone lysines. The Ubp8/Sgf11/Sus1 module functions in H2B deubiquitination as well as mRNA export through interaction with pores within the nuclear membrane. Ada2 and Ada3, as well as Sca7, Taf12, and Chd1 function, in part, to regulate Gcn5-mediated HAT activity. The Spt3/Spt8 module interacts with the TATA-binding protein (TBP), and TBP and SAGA together interact strongly with the general transcription factor TFIIA and the elongation factor TFIIS. The histone H3 N-terminal tail is shown to illustrate interaction of SAGA with multiple resides, indicated by position number, within the peptide. Dotted lines indicate interactions, while arrows indicate enzymatic activities.