An integrated SAGA and TFIID PIC assembly pathway selective for poised and induced promoters

In this study, Mittal et al. report that sequence-specific transcription factors and their tethered cofactors (e.g., SAGA, Mediator, TUP, NuA4, SWI/SNF, and RPD3-L) are generally bound to promoters prior to induction (poised), rather than recruited upon induction, whereas induction recruits the preinitiation complex (PIC) to DNA. Their findings suggest that inducible systems, where present, evolved on top of constitutive systems. Genome-wide, little is understood about how proteins organize at inducible promoters before and after induction and to what extent inducible and constitutive architectures depend on cofactors. We report that sequence-specific transcription factors and their tethered cofactors (e.g., SAGA [Spt-Ada-Gcn5-acetyltransferase], Mediator, TUP, NuA4, SWI/SNF, and RPD3-L) are generally bound to promoters prior to induction (poised), rather than recruited upon induction, whereas induction recruits the preinitiation complex (PIC) to DNA. Through depletion and/or deletion experiments, we show that SAGA does not function at constitutive promoters, although a SAGA-independent Gcn5 acetylates +1 nucleosomes there. When inducible promoters are poised, SAGA catalyzes +1 nucleosome acetylation but not PIC assembly. When induced, SAGA catalyzes acetylation, deubiquitylation, and PIC assembly. Surprisingly, SAGA mediates induction by creating a PIC that allows TFIID (transcription factor II-D) to stably associate, rather than creating a completely TFIID-independent PIC, as generally thought. These findings suggest that inducible systems, where present, are integrated with constitutive systems.

Automated summary

In this study, researchers found that specific sequence transcription factors and their cofactors are bound to promoters prior to induction, rather than recruited upon induction. Induction recruits the preinitiation complex to DNA. This suggests that inducible systems are integrated with constitutive systems.