Fig. 3.

Functions of CTCF in transcriptional regulation and impact of perturbed CTCF binding in cancer cells. A: TAD insulation, enhancer-promoter looping and heterochromatin barrier function through CTCF binding. A schematic Hi-C map with 3 TADs and simulated CTCF, Rad21 (cohesin complex) and H3K27me3 ChIP-seq are depicted. The yellow gene (center TAD) is inactive because of the enhancer-blocking activity of CTCF at the TAD boundary. The green gene on the right is activated by its enhancer though DNA loop formation. B: Schematic chromatin organization of the 3 TADs from panel A, showing the relative position between neighboring TADs, the containment of heterochromatin and the physical proximity between the green gene and its enhancer at loop anchors mediated by CTCF and the cohesin complex. C: Consequence of changes in the DNA sequence or methylation status of a CBS on TAD structure. Perturbation of CTCF binding at the CBSs that separate TAD 2 and TAD 3 (purple arrow) causes a fusion between the domains. This allows the hijacking of the enhancer located in former TAD 3 by the gene previously located in TAD 2. D: Schematic chromatin organization of the TADs from panel C. TAD 2 and 3 have fused, with the disruption of the boundary causing enhancer hijacking and gene activation. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)