Fig. 4: The H3K9me3 mark operates as a central, outcome-relevant senescence relay.

a Western blot analysis of senescence-related proteins in Bcl2-protected LSD1- or JMJD2C-overexpressing, Suv39h1-deficient and control lymphomas after 5 days of ADR treatment in vitro or left untreated. Samples are representative of each genotype (n > 3). Original photomicrographs are presented in Supplementary Fig. 8. b Lymphoma sections of CTX-treated mice bearing Bcl2-protected JMJD2C- or LSD1-overexpressing vs. control lymphomas stained for SA-β-gal. Numbers indicate mean percentages of cells positive ± s.d. (shown are representative photomicrographs of biological replicates, n = 4 primary lymphomas for control;untreated, n = 5 for control;CTX, n = 3 for LSD1;untreated, n = 4 for LSD1;CTX, n = 4 for JMJD2C;untreated, n = 4 for JMJD2C;CTX). c Overall survival (OS) in CTX-treated mice bearing Bcl2-protected JMJD2C (n = 11, orange line)-, LSD1 (n = 10, blue line)-overexpressing or control (n = 14, black line) lymphomas. d Tumor sections of CTX- or CTX-plus-2-PCPA-1a-treated mice bearing lymphomas with low or high H3K9-active demethylases (GO:0032454) expression levels stained for SA-β-gal. Numbers indicate mean percentages of cells positive ± s.d. (shown are representative photomicrographs of n = 3 biological replicates per group). “*” represents statistical significance by unpaired t test, p = 0.0129 (high;CTX vs. high;CTX + 2-PCPA-1a) or p = 0.0339 (high;CTX vs. low;CTX). e Tumor-free survival of CTX-treated mice stratified by median expression of genes that belong to the GO term “histone demethylase activity (H3-K9 specific)” (GO:0032454). Two mice per lymphoma were used. Above median: n = 37 (black line), below median: n = 39 (grey line). f Progression-free survival (PFS) of elderly (>63 years; with their aged and presumably more senescence-prone lymphoma cells) R-CHOP-treated DLBCL patients (GSE31312) stratified as in (e). Above median: n = 116 (black line), below median: n = 117 (grey line). g Tumor-free survival of CTX-treated mice bearing Eµ-myc lymphomas with high (n = 28, black line) or low (n = 31, grey line) levels of the H3K9me3 mark. h OS of R-CHOP-treated DLBCL patients bearing lymphoma with high (n = 18, black line) or low (n = 17, grey line) levels of the H3K9me3 mark. All scale bars in this figure represent 100 µm.