The SAGA complex regulates early steps in transcription via its deubiquitylase module subunit USP22

Timothy J. Stanek, Victoria J. Gennaro, Mason A. Tracewell, Daniela Di Marcantonio, Kristen L. Pauley, Sabrina Butt, Christopher McNair, Feng Wang, Andrew V. Kossenkov, Karen E. Knudsen, Tauseef Butt, Stephen M. Sykes, Steven B. McMahon

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The SAGA coactivator complex is essential for eukaryotic transcription and comprises four distinct modules, one of which contains the ubiquitin hydrolase USP22. In yeast, the USP22 ortholog deubiquitylates H2B, resulting in Pol II Ser2 phosphorylation and subsequent transcriptional elongation. In contrast to this H2B-associated role in transcription, we report here that human USP22 contributes to the early stages of stimulus-responsive transcription, where USP22 is required for pre-initiation complex (PIC) stability. Specifically, USP22 maintains long-range enhancer–promoter contacts and controls loading of Mediator tail and general transcription factors (GTFs) onto promoters, with Mediator core recruitment being USP22-independent. In addition, we identify Mediator tail subunits MED16 and MED24 and the Pol II subunit RBP1 as potential non-histone substrates of USP22. Overall, these findings define a role for human SAGA within the earliest steps of transcription.

Original languageEnglish
Article numbere102509
JournalEMBO Journal
Volume40
Issue number16
DOIs
StatePublished - Aug 16 2021

Keywords

  • SAGA
  • USP22
  • epigenetic
  • pre-initiation complex
  • transcription

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