1. The SAGA complex regulates early steps in transcription via its deubiquitylase module subunit USP22.
- Author
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Stanek TJ, Gennaro VJ, Tracewell MA, Di Marcantonio D, Pauley KL, Butt S, McNair C, Wang F, Kossenkov AV, Knudsen KE, Butt T, Sykes SM, and McMahon SB
- Subjects
- Apoptosis, Endoplasmic Reticulum Stress genetics, HCT116 Cells, Humans, Mediator Complex genetics, Promoter Regions, Genetic, RNA Polymerase II, Transcription, Genetic, Ubiquitin Thiolesterase genetics
- 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., (© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
- Published
- 2021
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