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CREs are binding sites for transcription factors (TFs), which bring together enhancers and their target gene promoters. De novo recruitment of transcriptional machinery including RNA polymerase II (RNA Pol II) and co-factors leads to transcription of the target gene. RNA Pol II can be bound to gene promoters and enhancers in a poised state. Through recruitment of release factors, poised promoters become active to allow transcriptional activation. Regulatory activity can be achieved through transcription of non-coding RNAs, which can modulate chromatin-modifying enzymes, influence local transcription regulators, or promote the formation of multi-molecular assemblies in the nucleus. Enhancer-promoter communication is dynamic, and gene activity is not always correlated with protein- or RNA-mediated spatial proximity.

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