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

Genes Dev. 2022 Sep 1;36(17-18):985-1001. doi: 10.1101/gad.350026.122. Epub 2022 Oct 27.


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.

Keywords: ChIP-seq; SAGA; Saccharomyces; gene regulation; genomics; transcription preinitiation complex.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Promoter Regions, Genetic / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factor TFIID* / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Transcription Factor TFIID
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Nucleosomes
  • Transcription Factors
  • Histone Acetyltransferases
  • NuA4 protein, S cerevisiae