@article{b6d07fda661d4bd98a895fafc71339c1,
title = "The SAGA complex regulates early steps in transcription via its deubiquitylase module subunit USP22",
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.",
keywords = "SAGA, USP22, epigenetic, pre-initiation complex, transcription",
author = "Stanek, {Timothy J.} and Gennaro, {Victoria J.} and Tracewell, {Mason A.} and {Di Marcantonio}, Daniela and Pauley, {Kristen L.} and Sabrina Butt and Christopher McNair and Feng Wang and Kossenkov, {Andrew V.} and Knudsen, {Karen E.} and Tauseef Butt and Sykes, {Stephen M.} and McMahon, {Steven B.}",
note = "Funding Information: These studies were supported in part via NIH grants R01CA182569 (to KEK and SBM) and F31CA165475 (to TJS). We gratefully acknowledge B.F. Pugh (Penn State University) for providing advice and Jonathan Ruffin (IQVIA) for providing bioinformatics analysis. FW and TB are employed by Progenra Inc., a biotech company engaged in targeting DUBs for therapeutic benefit. The National Cancer Institute‐supported SKCC Flow Cytometry and Cancer Genomics facilities and the Wistar Bioinformatics facility were used in these studies. Funding Information: These studies were supported in part via NIH grants R01CA182569 (to KEK and SBM) and F31CA165475 (to TJS). We gratefully acknowledge B.F. Pugh (Penn State University) for providing advice and Jonathan Ruffin (IQVIA) for providing bioinformatics analysis. FW and TB are employed by Progenra Inc., a biotech company engaged in targeting DUBs for therapeutic benefit. The National Cancer Institute-supported SKCC Flow Cytometry and Cancer Genomics facilities and the Wistar Bioinformatics facility were used in these studies. Publisher Copyright: {\textcopyright} 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license",
year = "2021",
month = aug,
day = "16",
doi = "10.15252/embj.2019102509",
language = "English",
volume = "40",
journal = "EMBO Journal",
issn = "0261-4189",
number = "16",
}