SAGA-CORE subunit Spt7 is required for correct Ubp8 localization, chromatin association and deubiquitinase activity

13 páginas, 5 figuras, 1 tabla. Contiene información suplementaria en: Supplementary information accompanies this paper at https://doi.org/10.1186/s13072-020-00367-3Background: 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.This study was supported by funds to SR-N from the Spanish MINECO, MICIIN (BFU2014-57636, BFU2015-71978, PGC2018-099872-B-I00) and the Generalitat Valenciana (PROM/2012/061, ACOMP2014/061 and PROMETEO 2016/093). This work was supported by FEDER 2014–2020 and the Ministerio de Economia y Competitividad (MINECO) of Spain. V.G-M was supported by the FPU program from the Ministerio de Educación y Ciencia (AP2009-0917); C.C-N by the Generailtat Valenciana PROMETEO/2016/093; P.O-C by the FPI program from MINECO (BES2012-058587); and M.M-E by the GVA (Val I+D: ACIF/2015/025). The M.I-V lab was co-funded by European Regional Development Funds (ERDF) and the Horizon 2020 Framework Programme of the European Union under the grant agreement 688945 (Euro-BioImaging Prep Phase II).Peer reviewe

RENACER study: Assessment of 12-month efficacy and safety of 168 certolizumab PEGol rheumatoid arthritis-treated patients from a Spanish multicenter national database

Objective: To assess effectiveness and safety of certolizumab PEGol (CZP) in rheumatoid arthritis (RA) patients after 12 months of treatment and to detect predictors of response.Methods: Observational longitudinal prospective study of RA patients from 35 sites in Spain. Variables (baseline, 3- and 12-month assessment): sociodemographics, previous Disease Modifying Anti-Rheumatic Drug (DMARD) and previous Biological Therapies (BT) use; TJC, SJC, ESR, CRP, DAS28, SDAI. Response variables: TJC, SJC, CRP, ESR, and steroids dose reductions, EULAR Moderate/Good Response, SDAI response and remission, DAS28 remission. Safety variables: discontinuation due to side-effects. Descriptive, comparative and Logistic regression analyses were performed.Results: We included 168 patients: 79.2% women, mean age 54.5 years (+/- 13.2 SD), mean disease duration 7.5 years (+/- 7.3 SD). Mean number of prior DMARD: 1.4 (+/- 1.2 SD), mean number of prior BT was 0.8 (+/- 1.1). Mean time on CZP was 9.8 months (+/- 3.4 SD). A total of 71.4% were receiving CZP at 12-month assessment. Baseline predictors of response: lower prior number DMARD; low number prior BT; higher CRP, ESR, TJC, SJC, DAS28 and SDAI (

Infective Endocarditis in Patients on Chronic Hemodialysis

International audienceInfective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD)