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. Author manuscript; available in PMC: 2023 Aug 4.
Published in final edited form as: Mol Cell. 2022 Jun 2;82(15):2738–2753.e6. doi: 10.1016/j.molcel.2022.05.010

Figure 6. Defective RNAPII Transcription Promotes Gene Fusions.

Figure 6.

(A) The correlation between the indicated gene or complex expression levels and the number of gene fusions per sample was analyzed in the indicated TCGA datasets. The results were shown as the ratio of the average of gene fusions in high to low groups. A significant ratio over 1 indicates that the high expression of the gene of interest is associated with a higher number of gene fusions, while a ratio below 1 indicates that the low expression of the gene of interest is associated with the higher number of gene fusions. The significant correlation is shown in red. See also Table S2.

(B) A schematic representation of the system for chromosomal translocation detection using the U2OS AsiSI cell line. The timeline of experiments is shown.

(C) The approximate position of MIS12 and TRIM37 on Chr 17 and the log2 ratio of UBF TSA-seq signals (THZ1/DMSO) and Compartment A/B scores at these loci are shown.

(D) The effect of THZ1, DRB, or Triptolide treatment on the frequency of MIS12-TRIM37 fusion was analyzed (mean with 95% CI, n=10, 18, 6, left to right, for data points from more than four biological replicates).

(E) The approximate position of PIP5KL1, NR6A1, GNE, and LINGO2 on Chr 9 and the log2 ratio of UBF TSA-seq signals (THZ1/DMSO) and Compartment A/B scores at these loci are shown.

(F) The effect of THZ1 treatment on the frequency of intra-chromosome gene fusion between Compartment A-A (PIP5KL1-NR6A1, PIP5KL1-GNE) and Compartment A-B (PIP5KL1-LINGO2) was analyzed (mean with SEM, n=6 for data points of independent experiments).

(G) The effect of THZ1 treatment on the frequency of inter-chromosome gene fusion was compared between MIS12-ASXL1 and MIS12-SLC32A1 (mean with SEM, n=10, 12, left to right, for data points of independent experiments).

(H) The effect of THZ1 treatment on MIS12-RASA3 fusion and MIS12-NGR fusion was analyzed as in (G). (mean with SEM, n=11, 10, left to right, for data points of independent experiments). The approximate position of RASA3 and NGR on Chr 13 and the log2 ratio of UBF TSA-seq signals (THZ1/DMSO) and Compartment A/B scores at these loci are shown left.