Fig. 5: PSPC1 co-condensates with NONO-TFE3 to recruit RNAPII. | Nature Communications

Fig. 5: PSPC1 co-condensates with NONO-TFE3 to recruit RNAPII.

From: RNA-mediated condensation of TFE3 oncofusions facilitates transcriptional hub formation to promote translocation renal cell carcinoma

Fig. 5

a Heatmaps showing the binding of NONO-TFE3, PSPC1, RNAPII-total, RNAPII-Ser5p (Pol II-S5), RNAPII-Ser2p (Pol II-S2), H3K27ac and H3K4me3 from −2 kb TSS to +2 kb TES at 5,011 genes occupied by NONO-TFE3. b Venn diagram showing the overlapping genes occupied by NONO-TFE3 and PSPC1 in UOK109 KI cells (left) and overlapping differentially expressed genes (DEGs) identified from RNA-seq in UOK109 KI cells treated with DMSO or dTAG-13 for 24 h (NONO-TFE3 regulated genes) or UOK109 KI cell with and without PSPC1 knocking down (KD) (PSPC1 regulated genes) (right). c Gene set enrichment analysis of overlapped DEGs (n = 500) identified from (b) in tRCC patient sample cohorts41. d Representative images (left) and quantification (right) of clone formation assay for UOK109 KI cells treated with DMSO or inhibitors against HK2 (HK2 i) or RRM2 (RRM2 i). n = 3 independent biological replicates; one-way ANOVA with Tukey’s post-hoc test. Data are shown as mean ± SD. e Genome browser views of the indicated sequencing results at representative loci in UOK109 KI cells upon treatments. n = 2 independent biological replicates. f Metagene binding profiles of RNAPII-total in control (shScramble, black line) and PSPC1KD (shPSPC1, red line) UOK109 KI cells at NONO-TFE3 regulated (left, n = 500) or non-regulated genes (right, n = 10,113) (from −2 kb TSS to +2 kb TES) identified from RNA-seq. g Metagene binding profiles of RNAPII-total (Pol II-total), RNAPII-Ser5p (Pol II-S5), RNAPII-Ser2p (Pol II-S2) in DMSO (black line) or dTAG-13 treated (500 nM, 4 h, red line) UOK109 KI cells at NONO-TFE3 regulated (left, n = 500) or non-regulated genes (right, n = 10,113) (from −2 kb TSS to +2 kb TES) identified from RNA-seq. h Binding enrichment of PSPC1, RNAPII-total, RNAPII-Ser5p (Pol II-S5), RNAPII-Ser2p (Pol II-S2) at NONO-TFE3 target (n = 115) or non-target genes (n = 4896) identified from SLAM-seq. The box plots indicated the median (center line), the third and first quartiles (box limits) and 1.5x interquartile range (IQR) above and below the box (whiskers). (n = 2 independent biological replicates; two-sided Wilcoxon test). Source data are provided as a Source Data file.

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