Fig. 1
From: SETD1A protects from senescence through regulation of the mitotic gene expression program
SETD1A expression protects cells from senescence. a SETD1A is amplified in breast cancer. Publicly available data from 935 breast cancers (http://www.cbioportal.org/) was evaluated for SETD1A gene amplification. The frequency of amplification in mixed ductal and lobular (MDLC), invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILB) of the breast is shown. IBC represents invasive breast carcinoma. Clonal evolution of breast cancer patient derived xenografts in mice, studied at single-cell resolution21, shows that 24% of the resulting tumors exhibit SETD1A gene amplification (BCCRC-Xeno). Source data are provided as a Source Data file. b Kaplan–Meier analysis was used to plot the overall survival of hormone receptor positive breast cancer patients with high (upper tertile) and low SETD1A expression. p value was calculated using log-rank test (Logrank p = 0.0035; HR = 5.03 (1.51–16.8). c SETD1A depletion induces senescence. Left: Relative proliferation of MDA-MB-231 cells infected with shGFP and shSETD1A. shSETD1Aav represents the mean of cells infected with two different shSETD1A constructs. Data from three independent experiments are presented as Mean + SD; *p < 0.05 by two-tailed unpaired Student’s t test. Source data are provided as a Source Data file. Right: Images of ß-gal stained control (shGFP) and SETD1A-KD (shSETD1A) MDA-MB-231 cells are shown. The scale bar represents 50 µm. d Bar graph shows the percentage of ß-gal positive cells in MDA-MB-231 cultures infected with shSETD1A and shGFP. shSETD1Aav represents the mean of cells infected with two different shSETD1A constructs. Data from three independent experiments are presented as Mean + SD; *p < 0.05 by two-tailed unpaired Student’s t test. Source data are provided as a Source Data file. e Senescence-associated secretory phenotype (SASP) in SETD1A-KD cells. RNAs showing log2 fold change > 1(FDR q value > 10%) in both SETD1A-KD (compared with shGFP) MDA-MB-231 and A549 cells were analyzed by GSEA for the enrichment of cytokine and chemokine activity. Genes contributing to the enrichment of each pathway and FDR q-values are provided. f Proteomic analysis of SASP in SETD1A-KD cells. Proteins showing log2 fold change > 1(FDR q value > 10%) in both SETD1A-KD (compared with shGFP) MDA-MB-231 and A549 cells were analyzed by GSEA for the enrichment of cytokine and chemokine activity. The fold induction of the genes contributing to the enrichment of each pathway and FDR q-values are provided
