Fig. 8. Promoter/enhancer interactions during metabolic adaptation to diet.

a, b Diet-induced differential gene expressions involves two types of promoter–enhancer interactions: de novo formation of promoter–enhancer interactions (a); activation of preformed promoter–enhancer interactions (b). c Enhancer activation can occur through multiple mechanisms. Nuclear receptors, including Hnf4α, can be activated by ligand binding, leading to local increases in histone acetylation and enhancer function (left panel). Alternatively, lineage-specifying transcription factors, including HNF4α, can bind constitutively at signal responsive enhancers and co-bind with other transcription factors, such as C/EBPα to regulate metabolism-related genes (right panel).