Enhancers, phase separation and the RNA polymerase II transfer model

The phenomenon of phase separation, the formation of highly concentrated regions of proteins and nucleic acids that have no separating membrane, is now recognised as an important mechanism for regulating gene expression through enhancer function. The ‘RNA polymerase II (PolII) transfer model’ was proposed as a mechanism for transcriptional activation at enhancers (for a definition of terms, please see Box 1).[1] The model specifically addresses how enhancers increase gene expression via phase separation, relying on transient transcription at enhancers to facilitate early release of transcription complexes. The model postulated that elongation-competent transcription complexes are assembled at enhancers during transcription of enhancer RNAs (eRNAs). These complexes are subsequently released in a dephosphorylated form and sequestered to the promoter via condensation, providing a model for initiation of gene transcription through phase separation at enhancers.[1] Although intriguing, at the time the model lacked supporting data. Here, we evaluate the PolII transfer model as a mechanism for enhancer condensate gene expression, in light of recent advances.