SAGA binds TBP via its Spt8 subunit in competition with DNA: implications for TBP recruitment.

In yeast, the multisubunit SAGA (Spt-Ada-Gcn5-acetyltransferase) complex acts as a coactivator to recruit the TATA-binding protein (TBP) to the TATA box, a critical step in eukaryotic gene regulation. However, it is unclear which SAGA subunits are responsible for SAGA's direct interactions with TBP and precisely how SAGA recruits TBP to the promoter. We have used chemical crosslinking to identify Spt8 and Ada1 as potential SAGA subunits that interact with TBP, and we find that both Spt8 and SAGA bind directly to TBP monomer in competition with TBP dimer. We further find that Spt8 and SAGA compete with DNA to bind TBP rather than forming a triple complex. Our results suggest a handoff model for SAGA recruitment of TBP: instead of binding together with TBP at the TATA box, activator-recruited SAGA transfers TBP to the TATA box. This simple model can explain SAGA's observed ability to both activate and repress transcription.