Fig. 6: Inverted repeat Alu SINEs are derepressed by co-inhibition of DNMT and HDAC in GP5d and OE19 cells. | Communications Biology

Fig. 6: Inverted repeat Alu SINEs are derepressed by co-inhibition of DNMT and HDAC in GP5d and OE19 cells.

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

Fig. 6

a Boxplots showing a comparison of expression of transcriptionally active IR-Alu SINEs (total sum of RNA-seq reads for DMSO and DNMTi-HDACi ≥ 5, see “Methods” for details) in DMSO and DNMTi-HDACi GP5d, OE19, and GP5d p53-KO cells. Majority of IR-Alu SINEs are derepressed by DNMTi-HDACi (two-sided Wilcoxon paired test). 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 Heatmap showing the ChIP-seq signal for H3K27ac at IR-Alu SINEs in DMSO and DNMTi-HDACi GP5d and OE19 cells. c Comparison of normalized RNA-seq read counts for ADAR1 gene in DMSO and DNMTi-HDACi GP5d, OE19, and GP5d p53-KO cells. The graph shows mean ± SD values for three biological replicates (two-sided unpaired t-test). d Microscopy images for GP5d cells treated with DMSO or DNMTi-HDACi. DNA was stained with DAPI (blue), and dsRNA was stained using the J2 antibody (green). All scale bars are 20 μm. Cytoplasmic levels of dsRNA increased in DNMTi-HDACi treated GP5d cells as compared to the DMSO. e Microscopy images for dsRNA staining in OE19 cells treated with DMSO or DNMTi-HDACi, as shown in Fig. 6d. f Microscopy images for dsRNA staining in GP5d p53-KO cells treated with DMSO or DNMTi-HDACi, as shown in Fig. 6d. g Alu editing index (AEI) was calculated by using RNAeditingIndexer42 tool on RNA-seq data. Bar plots showing AEI for DMSO and DNMTi-HDACi GP5d, OE19, and GP5d p53-KO cells. The graph shows mean ± SD values for three biological replicates (two-sided unpaired t-test). h Bar plots comparing RIG1 gene expression in DMSO and DNMTi-HDACi GP5d, OE19, and GP5d p53-KO cells. The graph shows mean ± SD values for three biological replicates (two-sided unpaired t-test). i qRT-PCR data showing RIG-I mRNA expression in GP5d and OE19 cells treated with DMSO and DNMTi-HDACi (GAPDH normalized). The graph shows mean ± SD values for three biological replicates. Source data are provided as Supplementary Data 11.

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