The schematics of example pathogenic mechanisms in the 3D genome. (A) Abnormal expansion of CGG-repeat to the length > 200 in FMR1 represses its expression in fragile X syndrome. (B-E) Several mechanisms are involved in reorganizing 3D genome architecture in cancers, such as (B) transposable elements containing CTCF-binding sites move around and change the genome topology, or (C) oncogenes may acquire super-enhancers during cancer development, or (D) disrupted CTCF-mediated insulation allows the proto-oncogene to form de novo interaction with the active enhancer, thus, promotes its transcription, or (E) complex interactions between super-enhancers and an oncogene mediated by master hub activates the oncogene expression. Solid blue lines indicates the interactions between the loci. (F) Impaired cohesin binding to the genome delays the cell cycle and eventually causes Cornelia de Lange syndrome. (G) A big TAD is partitioned into many smaller TADs during T cell activation.
