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Fig. 3 | Genome Medicine

Fig. 3

From: DNA methylation-based chromatin compartments and ChIP-seq profiles reveal transcriptional drivers of prostate carcinogenesis

Fig. 3

Analysis of transcription factor DNA binding profiles in the context of aberrant chromatin compartmentalization in prostate adenocarcinoma. a Degree of enrichment or depletion of TF ChIP-seq peak sites in the set of regions with PRAD-specific open chromatin compartmentalization. Each ENCODE ChIP-seq study has a corresponding data point, and they are ranked along the horizontal axis by the degree of enrichment (from most depleted on the left to most enriched on the right). Vertical axis gives log ratio of the observed over expected number of peaks lying in the regions of PRAD-specific open chromatin (i.e. windows assigned to the open chromatin compartment in tumours but the closed chromatin compartment in normal tissue). Dotted horizontal line at 0 indicates number of peaks in PRAD-specific open chromatin is exactly that expected by chance. b Heatmap showing overlap between peak locations for each of the most PRAD-specific open chromatin enriched TF ChIP-seq studies. Black indicates no overlap, white indicates total overlap. c Scatter-plot showing the relationship between a TF’s enrichment to PRAD-specific open chromatin and target gene overexpression in PRAD relative to normal prostate tissue. Horizontal axis gives log ratio of observed over expected number of peaks lying in PRAD-specific open chromatin (as in a) for each ENCODE TF ChIP-seq study. Vertical axis gives –log10 p value from test of systematic overexpression of inferred target genes of the corresponding TF (genes with ChIP-seq peak lying within 5 kb of TSS) in PRAD tumours relative to normal prostate tissues. Dashed red lines indicate the median value in each axis across all the included ENCODE TF ChIP-seq studies. d Volcano plot showing differential expression of candidate driver TFs in the context of all genes’ differential expression between PRAD tumours and normal prostate tissue. Horizontal axis gives log2 ratio between median expression in PRAD tumours and median expression across normal prostate tissues. Vertical axis gives –log10 p value of differential expression as evaluated through empirical Bayes moderated t test. Candidate drivers with ChIP-seq studies suggesting the TF’s DNA binding sites are enriched in regions of PRAD-specific open chromatin are shown in red, candidate driver (TRIM28) with ChIP-seq studies suggesting the TF’s DNA binding sites are enriched in regions of PRAD-specific closed chromatin is shown in blue

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