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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 , McMahon SB
The SAGA complex regulates early steps in transcription via its deubiquitylase module subunit USP22
EMBO J. 2021 Aug 16;40(16) :e102509
PMID: 34155658    PMCID: PMC8365265    URL: https://www.ncbi.nlm.nih.gov/pubmed/34155658
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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.
1460-2075 Stanek, Timothy J Orcid: 0000-0001-9192-4978 Gennaro, Victoria J Tracewell, Mason A Di Marcantonio, Daniela Pauley, Kristen L Butt, Sabrina McNair, Christopher Wang, Feng Kossenkov, Andrew V Knudsen, Karen E Orcid: 0000-0002-1301-890x Butt, Tauseef Sykes, Stephen M McMahon, Steven B Orcid: 0000-0002-3405-1768 R01CA182569/HHS|NIH|National Cancer Institute (NCI)/ F31CA165475/HHS|NIH|National Cancer Institute (NCI)/ Journal Article England EMBO J. 2021 Jun 22:e102509. doi: 10.15252/embj.2019102509.