Figure 1. Schematic diagram of regulatory re-wiring following the deletion of a domain boundary.

( A) Interactions between enhancers and their target genes occur within chromatin domains. The deletion of a boundary region leads to novel gene-enhancer interactions between previously insulated elements; this process may lead to the spatial or temporal mis-expression of genes. ( B) The same scenario as in ( A) is drawn as represented by a high-throughput chromosome conformation capture (Hi-C) interaction map. Red triangles: topologically associating domains; yellow boxes: regulatory elements; blue boxes: target genes; green circles: insulator elements. Further examples of pathogenic genomic rearrangements, including insulator-spanning tandem duplications, are illustrated in 31.