Figure 3. Mediator regulates chromatin architecture.

The cooperative interactions between Mediator and transcription factors (TF), cohesin and non-coding RNAs (ncRNA) appear to stabilize enhancer-promoter loops102,134,139,140. An expanding set of factors influence the formation and stability of enhancer-promoter loops1 and the formation of such structures correlates with high levels of transcription125-127. Because the CDK8 module must dissociate from Mediator to allow pol II–Mediator binding18,19, a potential ncRNA–CDK8 module interaction, perhaps via the CDK8 module subunit MED12134, may tether the CDK8 module near the PIC. This could facilitate re-formation of CDK8-Mediator complexes following pol II promoter escape.