Fig. 7: SETDB1i and DNMTi-HDACi increases TE-chimeric transcript expression and activates inflammatory response. | Communications Biology

Fig. 7: SETDB1i and DNMTi-HDACi increases TE-chimeric transcript expression and activates inflammatory response.

From: Cancer cell type-specific derepression of transposable elements by inhibition of chromatin modifier enzymes

Fig. 7

a SETDB1i/KO increases the expression of TE-chimeric transcripts. Boxplots show the expression of TE-chimeric transcripts in A375, GP5d, OE19, and GP5d p53-KO cells with and without SETDB1i/KO. Expression of TE-chimeric transcripts was analyzed with the TEprof2 pipeline16. P-values were calculated with a two-sided Wilcoxon test (n = 53, 24, 144, and 141 differentially expressed TE-chimeric transcripts in A375, GP5d, GP5d p53-KO, and OE19, respectively). The lower and upper hinges of the boxes represent the 25th to 75th percentiles, the midline is the median, and the whiskers extend from the hinges to the minimum and maximum values by 1.5 * IQR. b Analysis of TE subfamilies from which the TE-chimeric transcripts are derived from upon SETDB1i/KO. The counts for TE-chimeric transcripts are log2-transformed. c DNMTi-HDACi increases the expression of TE-chimeric transcripts. Boxplots show the expression of TE-chimeric transcripts in DMSO and DNMTi-HDACi GP5d, GP5d p53-KO, and OE19 cells. P-values were calculated with a two-sided Wilcoxon test (n = 35, 175, and 193 for GP5d, OE19, and GP5d p53-KO cells, respectively). The boxplot features are as in Fig. 7a. d Cell type-specific expression of TE subfamilies forming TE-chimeric transcripts by DNMTi-HDACi in cancer cell lines. The counts for TE-chimeric transcripts are log2-transformed. e ISGs are upregulated by DNMTi-HDACi. ISG log2FCs are plotted for DNMTi-HDACi treated GP5d, OE19 and GP5d p53-KO cells. f SETDB1i and DNMTi-HDACi increased levels of Serine 477 phosphorylated IRF7. Western blot compares Ser477-phospho-IRF7 and total IRF7 protein levels in GP5d, OE19 and GP5d p53-KO cells treated with different CME inhibitors. g qRT-PCR data showing IFNα mRNA expression in GP5d and OE19 cells treated with DMSO, DNMTi-HDACi, and SETDB1i (GAPDH normalized). ISGs are upregulated by DNMTi-HDACi and SETDB1i in GP5d and OE19 cells. The graph shows mean ± SD values for three biological replicates. Source data are provided as Supplementary Data 11.

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