Fig. 6

The USP22-specific DUBm of the SAGA complex mediates the OXPHOS gene expression program and respiratory capacity in TNBC: A Patient survival analysis show that in contrast to USP51 and USP27X, USP22 and ATXN7L3 correlate with a poor survival outcome in BLBC and HER2⁺-BC patients (source: https://portal.gdc.cancer.gov/). B USP22 and ATXN7L3 RNA levels correlate with cancer stem cell characteristics BLBC and HER2⁺-BC biopsies (source: https://www.cbioportal.org/). C USP22 and ATXN7L3 expression is associated with several OXPHOS-related transcriptomic signatures, based on the C2_REACTOME curated gene set collection (left panel). Respective GSEA profiles of the "REACTOME_MITOCHONDRIAL_BIOGENESIS" gene set are also shown (right panel). D-E Loss of ATXN7L3 leads to an impaired expression of OXPHOS-related genes (D) and a drop of the OCR (E) in TNBC cell lines. F Aggregate profiles of RNA polymerase II (RNApol2) occupancy at the transcriptional start site (TSS) OXPHOS-related (left profile) and randomly selected genes (right profile) and the respective quantification of TSS-associated RNApol2 occupancy in shControl- and shUSP22-treated HCT116 cells (right panel; accession number: GSE121798). Statistics: Student t-test. *p<0.05, **p<0.01, ***p<0.005. B: Pearson correlation analysis; C, D-F (based on the area under the curve = AUC): Student t-test. NES: Normalized Enrichment Score. All experiments were performed in biological triplicates