Visualization of endogenous enhancer-promoter interactions in a single nucleus through chromatin labeling.

Recent studies highlight the critical role of nuclear genome organization in regulating gene expression. Dynamic changes in the hierarchical structure of chromatin modulate transcription by influencing the recruitment of transcription factors and altering the epigenetic landscape. Among these regulatory mechanisms, enhancer-promoter (E-P) interactions are of particular importance. Enhancers physically interact with the promoters of target genes, a process mediated by various coactivators, which facilitates the transfer of enhancer-bound transcription factors and ultimately leads to transcriptional bursting. While next-generation sequencing techniques have provided significant insights into the features of E-P interactions, the effects of cell-to-cell heterogeneity and the physical dynamics of these interactions remain poorly understood due to the lack of spatiotemporal information. In this article, we introduce a platform that enables imaging-based approaches to visualize E-P interactions at the single-cell level.