Fig. 1From: From association to mechanism in complex disease genetics: the role of the 3D genomePredicting enhancer–promoter interactions using linear proximity versus 3D proximity. a Traditional modeling of enhancer function in the context of a linear genome where an enhancer (green triangle) is predicted to modulate the function of the promoter in closest linear proximity (gene 2 (blue rectangle) or gene 3 (yellow rectangle)). b Modeling in the context of the 3D genome where an enhancer (green triangle) often regulates distant gene expression through long-range DNA looping to the gene promoter (gene 1 (green rectangle)). Due to spatial proximity, the enhancer “skips” gene 2 (blue rectangle). Enhancer function is restricted within the insulated loop structure formed by a CTCF-CTCF (arrows)–cohesion (red ring) complex, and therefore cannot activate gene 3 (yellow rectangle) or gene 4 (red rectangle) despite close linear proximityBack to article page