SAGA-CORE subunit Spt7 is required for correct Ubp8 localization, chromatin association and deubiquitinase activity
Por:
C. NUNO-CABANES, V. GARCIA-MOLINERO, M. MARTIN-EXPOSITO, M. GAS, P. OLIETE-CALVO, E. GARCIA-OLIVER, M. DE LA IGLESIA-VAYA and S. RODRIGUEZ-NAVARRO
Publicada:
28 oct 2020
Resumen:
Background Histone H2B deubiquitination is performed by numerous deubiquitinases in eukaryotic cells including Ubp8, the catalytic subunit of the tetrameric deubiquitination module (DUBm: Ubp8; Sus1; Sgf11; Sgf73) of the Spt-Ada-Gcn5 acetyltransferase (SAGA). Ubp8 is linked to the rest of SAGA through Sgf73 and is activated by the adaptors Sus1 and Sgf11. It is unknown if DUBm/Ubp8 might also work in a SAGA-independent manner. Results Here we report that a tetrameric DUBm is assembled independently of the SAGA-CORE components SPT7, ADA1 and SPT20. In the absence of SPT7, i.e., independent of the SAGA complex, Ubp8 and Sus1 are poorly recruited to SAGA-dependent genes and to chromatin. Notably, cells lacking Spt7 or Ada1, but not Spt20, show lower levels of nuclear Ubp8 than wild-type cells, suggesting a possible role for SAGA-CORE subunits in Ubp8 localization. Last, deletion of SPT7 leads to defects in Ubp8 deubiquitinase activity in in vivo and in vitro assays. Conclusions Collectively, our studies show that the DUBm tetrameric structure can form without a complete intact SAGA-CORE complex and that it includes full-length Sgf73. However, subunits of this SAGA-CORE influence DUBm association with chromatin, its localization and its activity.
Filiaciones:
:
CSIC, Inst Biomed Valencia, Gene Express & RNA Metab Lab, C Jaume Roig 11, Valencia 46010, Spain
Ctr Invest Principe Felipe CIPF, Gene Express & RNA Metab Lab, C-E Primo Yufera 3, Valencia 46012, Spain
V. GARCIA-MOLINERO:
Ctr Invest Principe Felipe CIPF, Gene Express & RNA Metab Lab, C-E Primo Yufera 3, Valencia 46012, Spain
M. MARTIN-EXPOSITO:
CSIC, Inst Biomed Valencia, Gene Express & RNA Metab Lab, C Jaume Roig 11, Valencia 46010, Spain
Ctr Invest Principe Felipe CIPF, Gene Express & RNA Metab Lab, C-E Primo Yufera 3, Valencia 46012, Spain
M. GAS:
Ctr Invest Principe Felipe CIPF, Gene Express & RNA Metab Lab, C-E Primo Yufera 3, Valencia 46012, Spain
P. OLIETE-CALVO:
Ctr Invest Principe Felipe CIPF, Gene Express & RNA Metab Lab, C-E Primo Yufera 3, Valencia 46012, Spain
E. GARCIA-OLIVER:
Ctr Invest Principe Felipe CIPF, Gene Express & RNA Metab Lab, C-E Primo Yufera 3, Valencia 46012, Spain
:
Joint Unit FISABIO & Ctr Invest Principe Felipe C, Brain Connect Lab, C-E Primo Yufera 3, Valencia 46012, Spain
:
CSIC, Inst Biomed Valencia, Gene Express & RNA Metab Lab, C Jaume Roig 11, Valencia 46010, Spain
Ctr Invest Principe Felipe CIPF, Gene Express & RNA Metab Lab, C-E Primo Yufera 3, Valencia 46012, Spain
Gold, Green Published
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