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

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

The EMBO journal, 2021-08, Vol.40 (16), p.e102509-n/a [Periódico revisado por pares]

England: Blackwell Publishing Ltd

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Título:
The SAGA complex regulates early steps in transcription via its deubiquitylase module subunit USP22
Autor: Stanek, Timothy J ; Gennaro, Victoria J ; Tracewell, Mason A ; Di Marcantonio, Daniela ; Pauley, Kristen L ; Butt, Sabrina ; McNair, Christopher ; Wang, Feng ; Kossenkov, Andrew V ; Knudsen, Karen E ; Butt, Tauseef ; Sykes, Stephen M ; McMahon, Steven B
Assuntos: Apoptosis ; Chromatin ; Control stability ; Elongation ; Endoplasmic Reticulum Stress - genetics ; Enhancers ; epigenetic ; HCT116 Cells ; Histone H2B ; Histones ; Humans ; Hydrolase ; Initiation complex ; Mass spectrometry ; Mass spectroscopy ; Mediator Complex - genetics ; Modules ; Phosphorylation ; pre‐initiation complex ; Promoter Regions, Genetic ; Promoters ; Proteomes ; Recruitment ; RNA Polymerase II ; SAGA ; Substrates ; Tails ; transcription ; Transcription elongation ; Transcription factors ; Transcription, Genetic ; Ubiquitin ; Ubiquitin hydrolase ; Ubiquitin Thiolesterase - genetics ; USP22 ; Yeasts
É parte de: The EMBO journal, 2021-08, Vol.40 (16), p.e102509-n/a
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SourceType-Scholarly Journals-1
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Descrição: 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. SYNOPSIS In eukaryotic transcription, the SAGA coactivator subunit USP22 is commonly known for its deubiquitylation of histone H2B. Here, human USP22 is implicated in the earliest steps of transcription, where it plays a role in stabilizing the pre‐initiation complex. As part of SAGA, USP22 is directly required for initial transcription and overall biological consequences of the ER stress response. During stimulus‐responsive transcription, USP22 is not required for deubiquitylation of Ub‐H2B, but rather for stability of the pre‐initiation complex. Quantitative mass spectrometry of the ubiquitin‐modified proteome identifies non‐histone substrates of USP22 including Mediator tail subunits MED16 and MED24, and Pol II subunit RBP1. Loss of USP22 results in deficient Mediator tail‐module recruitment to target gene promoters, and alters the long‐range chromatin interaction landscape between promoters and enhancers. Loss of human USP22 affects the stability of the pre‐initiation complex, rather than histone H2B ubiquitylation, during stimulus‐responsive transcription.
Editor: England: Blackwell Publishing Ltd
Idioma: Inglês

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

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

England: Blackwell Publishing Ltd

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