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. Author manuscript; available in PMC: 2020 Oct 13.
Published in final edited form as: Nat Cell Biol. 2020 Apr 13;22(5):603–615. doi: 10.1038/s41556-020-0503-2

Fig. 7. LSD1 and BRD9 regulate an overlapping set of genes in MCC.

Fig. 7.

a. BRD9 degradation or inhibition partially rescues the reduced cell viability caused by LSD1 inhibition in MCC. MKL-1 cells were treated with DMSO, GSK-LSD1 (LSD1i, 0.1 μM), dBRD9 (1 μM), BRD9i (BI-7273, 1 μM), or combinations of LSD1i with dBRD9 or BRD9i for six days. The XTT assay was used to measure relative cell viability. Data are shown as mean of n=3 ± SD; two-sided t-test, *P<0.05, ****<0.00005. b. MKL-1 cells were treated with varying doses of GSK-LSD1 or dBRD9 for six days. SynergyFinder48 was used to calculate negative synergy (rescue) scores. c. RNA-seq was performed with two replicates of MKL-1 cells treated with DMSO, GSK-LSD1 (LSD1i, 0.1 μM), dBRD9 (0.1 μM), or both GSK-LSD1 and dBRD9 for six days. n=2. The heatmap shows expression changes in 1,111 genes induced by LSD1i in six virus-positive MCC cell lines (Fig. 3a-c and Source Data 7). d. DESeq2 counts of selected LSD1 target genes are shown. Multiple t-test was performed and p-valued were adjusted by FDR (See Supplementary Table 3). Data are shown as mean of n=2 ± SD. e. Selected GOTERM biological processes (BP), cellular components (CC), or KEGG -log10 of p-values for the pathways enriched with the Cluster 1 and 2 genes (Source Data 7). The clustering test was implemented using kappa statistics45. n=2. f. MKL-1 cells were treated with DMSO, LSD1i (GSK-LSD1, 0.05 μM), dBRD9 (1μM), BRD9i (BI-7273, 1 μM), LSD1i with dBRD9, or LSD1i with BRD9i for three days. The signals were normalized to the DMSO treated sample and RPLP0. Data are shown as mean of n=3 ± SD; two-sided t-test, *P<0.05; **<0.005; ***<0.0005.