Mechanism of enhancer–promoter action at a distance during active transcription

Determine the physical and molecular mechanism by which gene enhancers and promoters, which remain separated by approximately 150 nm during active transcription in Drosophila embryos, communicate to initiate and sustain transcriptional activity despite the absence of direct contact.

Background

Live fluorescence experiments in the early Drosophila embryo have measured distances between labeled promoter and enhancer elements and tracked transcriptional activity in real time. These studies show that transcription requires proximity between promoter and enhancer, yet higher-resolution imaging indicates that even when transcription is active the promoter and enhancer remain separated by around 150 nm.

This raises a fundamental question in gene regulation: how do regulatory elements exert functional influence across nanometer-scale separations in vivo? Resolving this mechanism is crucial for connecting spatial genome organization to transcriptional control.