Figure 5.

Differential interactions are enriched for enhancers, promoters, and CTCF-occupied genomic regions and may explain the unique epigenetic programs of normal and cancer cells. Chromatin interactions visualized in the Rondo interactive analysis tool. Anchor points of differential interactions are visualized simultaneously with ChIP-seq (H3K27ac, H3K4me1, H3K4me3), RefSeq genes, and RNA-seq data (circular tracks) inferring functionality (both active and repressive) of interactions. (A) In this example from Chr10:33,000,000–35,000,000, epigenetic remodeling (activation) of genes located at the differentially interacting region can be observed at 100-kb resolution. The promoter and a putative enhancer of the NRP1 gene are both marked by residual H3K4me1 in normal cells. Very little H3K4me3 (dark green) and H3K27ac (light green) is observed. (B) In contrast, these regulatory elements display a marked increase in H3K4me1, H3K4me3, and H3K27ac ChIP signal in PC3 prostate cancer cells, indicative of increased gene activity. This occurs concomitant with a new interaction depicted by the purple line in the cancer cells. (C) Genes at differential interaction anchor points are significantly overexpressed concomitant with a new interaction only present in the cancer cells (*q value < 0.0001).