Enhancer–promoter interactions and human disease.

(A) An inversion between GATA binding protein 2 (GATA2) and ecotopic viral integration site 1 (EVI1) repositions a GATA2 enhancer (green oval) near EVI1, leading to its ectopic expression while reducing GATA2 expression [65]. Inversion breakpoints are depicted by magenta and yellow dots. (B) The T-allele of rs12913832, which resides within an enhancer (green oval) of the oculocutaneous albinism II (OCA2) gene, leads to a stronger enhancer–promoter looping interaction versus the C allele, as observed by 3C [66]. (C) A 660 kb deletion that removes a TAD boundary and enhancer-A (Enh-A) leads to enhancer B (Enh-B) adoption by lamin B1 gene (LMNB1), leading to its misexpression and, subsequently, autosomal dominant adult-onset leukodystrophy (ADLD) [67]. Deletion breakpoints are depicted by magenta and yellow dots.