Fig. 1

A simplistic schematic for enhancer-mediated transcription activation. A pioneer TF binds a nucleosome at an enhancer and nucleates the process of enhancer priming, facilitating the recruitment of other TFs (ERα) and chromatin remodeling and modification factors (CR-MFs). ERα recruits the coactivators SRC-3 and p300, plus other TFs and coactivators as the MegaTrans complex. The Mediator complex and other relevant coactivators with distinct enzyme activities are subsequently recruited and their conformational changes result in transfer of the enhancer-bound coactivators onto the promoter-bound RNAPII complexes, establishing “transient and direct” enhancer-promoter contact (EPC). Sequential phosphorylation of the RNAPII C-terminal domain (CTD) at S5 and S2 residues coordinates transcription initiation and transition to elongation. Once the RNAPII exits the promoter for productive transcript elongation (mRNA), the Mediator/coactivators can enter another round of recruitment to the enhancer and subsequent transfer to the promoter, aided by EPC formation and severance, completing another cycle of RICE (collective “RNAPII/coactivator recruitment ➔ transcription initiation➔ promoter clearance ➔productive elongation” events). Similar actions by other TFs at the enhancer can amplify TF action, resulting in synergistic transcription activation. Not shown for simplicity: GTFs, RNAPII and eRNA transcription at the enhancer, and other factors and CR-MFs at the promoter