Dynamics of transcriptional enhancers and chromosome topology in gene regulation

Transcriptional enhancers are regulatory DNAs that instruct when and where genes should be transcribed in response to a variety of intrinsic and external signals. They contain a cluster of binding sites for sequence-specific transcription factors and co-activators to determine the spatiotemporal specificity of gene activities during development. Enhancers are often positioned in distal locations from their target promoters. In some cases, they work over a million base pairs or more. In the traditional view, enhancers have been thought to stably interact with promoters in a targeted manner. However, quantitative imaging studies provide a far more dynamic picture of enhancer action. Moreover, recent Hi-C methods suggest that regulatory interactions are dynamically regulated by the higher-order chromosome topology. In this review, we summarize the emerging findings in the field and propose that assembly of "transcription hubs" in the context of 3D genome structure plays an important role in transcriptional regulation.