Distinct regulatory mechanisms of eukaryotic transcriptional activation by SAGA and TFIID

Abstract

A growing number of human diseases are linked to abnormal gene expression which is largely controlled at the level of transcriptional initiation. The gene-specific activator promotes the initiation of transcription through its interaction with one or more components of the transcriptional initiation machinery, hence leading to stimulated transcriptional initiation or activation. However, all activator proteins do not target the same component(s) of the transcriptional initiation machinery. Rather, they can have different target specificities, and thus, can lead to distinct mechanisms of transcriptional activation. Two such distinct mechanisms of transcriptional activation in yeast are mediated by the SAGA (Spt-Ada-Gcn5-Acetyltransferase) and TFIID (Transcription factor IID) complexes, and are termed as "SAGA-dependent" and "TFIID-dependent" transcriptional activation, respectively. SAGA is the target of the activator in case of SAGA-dependent transcriptional activation, while the targeting of TFIID by the activator leads to TFIID-dependent transcriptional activation. Both the SAGA and TFIID complexes are highly conserved from yeast to human, and play crucial roles in gene activation among eukaryotes. The regulatory mechanisms of eukaryotic transcriptional activation by SAGA and TFIID are discussed here. This article is part of a Special Issue entitled The 26S Proteasome: When degradation is just not enough!

Figure 1

Schematic representations of SAGA and TFIID-dependent transcriptional activation. (A) The transcriptional activator that binds to the UAS of the promoter stimulates the formation of the PIC assembly at the core promoter through interaction with one or more components of the transcriptional initiation machinery, termed as “target”. The schematic representation of how different activator–target interactions stimulate TBP recruitment at the (B and C) SAGA and (D) TFIID-dependent promoters. Subsequent to TBP recruitment, formation of the PIC continues to initiate transcription [–4].

Figure 2

A model showing the role of the 19S RP in regulation of transcriptional activation of the GAL1 genes in vivo. The activator, Gal4p recruits SAGA to the GAL1 UAS through its interaction with Tra1p [27]. However, the targeting of SAGA to the GAL1 UAS is less efficient in the absence of the 19S RP [210]. The ATPase activity of the 19S RP enhances SAGA targeting to the GAL1 UAS in a positive feedback manner [210]. Similar enhancement of SAGA targeting has also been demonstrated by biochemical studies [207]. The 19S ATPase activity is also essential for recruitment of the Mediator complex [210]. Mediator is required for formation of the PIC [27]. Further, in support of this model, several interactions have been demonstrated by biochemical and genetic studies [, , , –213, 221]. For example, Lee et al. [207] have shown the physical and genetic interaction between SAGA and 19S RP. Sun et al. [221] have demonstrated the physical interaction between Mediator and the 19S RP. Functional and genetic interactions between SAGA and Mediator have also been reported [126, 127]. Further, several biochemical studies have shown the physical interaction of the 19S RP with the components of the PIC [–213]. However, whether these interactions occur directly in vivo remains to be investigated. “+” referes “stimulation”.

Figure 3

Schematic representations showing the destruction of the steroid receptors in a transcription-dependent manner. In the first round of transcriptional activation, receptor stimulates the assembly of GTFs to form the PIC, and then the component of the basal transcription machinery (e.g. the Cdk7 component of TFIIH) facilitates phosphorylation of the steroid receptor. Such phosphorylation triggers polyubiquitination of steroid receptor which is subsequently recognized and degraded by the 26S proteasome. SRE, steroid response element; p, phosphorylation; and Ub, ubiquitylation.