Mechanisms of enhancer action. Enhancer action on target promoters can occur via looping that enables physical contact in either a stable or dynamic manner in agreement with the evidence of proximity from chromatin conformation experiments and DNA FISH [ 39 ]. Alternative mechanism of action include the phase separation of enhancers, promoters, and associated proteins into condensates which can provide the proximity required for enhancer-promoter contact without looping [ 49 , 50 ]; the diffusion of factors from enhancers to promoters, such as acetylated TFs [ 51 ], forming a chemical gradient that enables specific targeting of promoters within close proximity without direct enhancer-promoter contact; and a role for eRNAs by triggering pause release of RNA Pol II at target promoters [ 54 ]
