Fig. 4. Chromatin activity profiles indicate the presence of the normal brain signature in pilocytic astrocytomas.

A, B Scatter-plots representing abundance of the H3K4me3 (A) and H3K27ac (B) marks obtained for PAs (X-axes) and DA/GBs (Y-axes). A single point on the scatter-plots represents an average abundance (ChIP-input) of a corresponding histone mark around a transcription start site [TSS + /-2 kb]. P values shown above the plots were estimated with the Wilcoxon rank-sum test. C Comparison of abundance values shown on 4A (X-axis) and 4B (Y-axis). The dashed frame indicates the strongest difference in H3K27ac abundance (top 10%) values. D Heatmaps showing H3K27ac abundance around the TSS for the top 10% regions (each row corresponds to a TSS, sorted by signal abundance). E ATAC-seq profiles of 4 PA samples and 4 DA/GB samples (see “Methods” for details) around TSS overlap with the regions selected on 4C. The blue and red lines correspond to PA and DA/GB samples, respectively. F Average H3K27ac profiles around TSS. The blue and red lines correspond to the top 10% regions selected in 4C and were computed for the PA and DA/GB samples, respectively. The gray lines correspond to regions not selected on 4C. The thick lines correspond to the average profiles, while colored areas give reference of the confidence interval for mean (CI). G Differences of the gene expression levels computed either for genes corresponding to the top 10% selected regions (left boxplot) or to the rest of the regions (right boxplot). P value shown above the plot and indicating differential regulation was estimated with the two-sided Wilcoxon rank-sum test. Data are represented as boxplots in which the box shows the quartiles of the dataset, the middle line is the median and the whiskers extends to the largest or smallest value no further than 1.5 × the inter-quartile range. H Results of Gene Ontology over-representation analysis performed for the genes corresponding to the top 10% regions. The barplot shows scaled Bonferroni corrected p values from the one-sided Fisher’s exact test and the vertical, dashed red line stands for the significance threshold (P = 0.05). I Logos of top DNA-binding motifs enriched in the top 10% regions. The enrichment was computed with regard to the rest of the analyzed regions. P values indicated above the logos stand for the significance of the enrichment and were computed with a tool from MEME-Suite (see “Methods” for details).