Proper enhancer–promoter interactions are essential to maintaining specific transcriptional patterns and preventing ectopic gene expression. Drosophila is an ideal model organism to study transcriptional regulation due to extensively characterized regulatory regions and the ease of implementing new genetic and molecular techniques for quantitative analysis. The mechanisms of enhancer–promoter interactions have been investigated over a range of length scales. At a DNA level, compositions of both enhancer and promoter sequences affect transcriptional dynamics, including duration, amplitude, and frequency of transcriptional bursting. 3D chromatin topology is also important for proper enhancer–promoter contacts. By working competitively or cooperatively with one another, multiple, simultaneous enhancer–enhancer, enhancer–promoter, and promoter–promoter interactions often occur to maintain appropriate levels of mRNAs. For some long-range enhancer–promoter interactions, extra regulatory elements like insulators and tethering elements are required to promote proper interactions while blocking aberrant ones. This review provides an overview of our current understanding of the mechanism of enhancer–promoter interactions and how perturbations of such interactions affect transcription and subsequent physiological outcomes.

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