Fig. 3
CDK12 inhibition leads to PCPA of long genes. a Average metagene profiles of normalized poly(A) 3′-seq reads at the transcription end sites (TES) (−1 to +4 kb) of all long genes (>64.5 kb) (left), and short genes (RD histone genes) (right). b Average metagene profiles of normalized poly(A) 3′-seq reads over gene bodies and extending −2 to +2 kb of all detected genes in cells treated with THZ531 400 nM for 2 and 6 h. Sense and antisense reads are depicted by solid and dashed lines, respectively. c Histograms showing the genomic distributions and rankings of the top 5000 poly(A) 3′-seq peaks in DMSO- and THZ531-treated cells (400 nM, 6 h). The poly(A) 3′ peaks were binned according to the depicted genomic regions and their intensities (x-axis). d Bar plot indicating the number of protein-coding genes that underwent premature cleavage and polyadenylation (PCPA) with THZ531. The expanded window on the right shows the genomic distribution of the identified intronic poly(A) sites. e Average metagene profiles of normalized poly(A) 3′-seq reads at the TSS (−1 to +10 kb) for all detected genes in Kelly WT (left) and Kelly E9R (right) cells. Changes (insets) in read density between DMSO- and THZ531 (200 nM, 6 h)-treated Kelly WT (p = 5.8e−41) and Kelly E9R (p = 0.11) cells; comparisons between groups by Wilcoxon rank-sum test. The center line indicates the median for each data set. f Density plot of odds-ratios of poly(A) site usage (intronic vs 3′ UTR) for genes in Kelly WT and E9R cells (p = 0, Kolmogorov-Smirnov test)
