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

Chitvan Mittal, Olivia Lang, William K M Lai, B Franklin Pugh

Genes & development 2022 Sep 01

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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. © 2022 Mittal et al.; Published by Cold Spring Harbor Laboratory Press.

Citation

Chitvan Mittal, Olivia Lang, William K M Lai, B Franklin Pugh. An integrated SAGA and TFIID PIC assembly pathway selective for poised and induced promoters. Genes & development. 2022 Sep 01;36(17-18):985-1001