Dynamic kissing model for enhancer-promoter communication on the surface of transcriptional condensates.

Abstract

Enhancer-promoter (E-P) communication is essential for gene transcription regulation in eukaryotes. Transcriptional condensates, which may form via liquid-liquid phase separation, are thought to enable E-P interactions. However, the kinetic mechanism of condensate-mediated E-P contacts and their effect on gene expression are unclear. Here we use a polymer physics-based model to investigate E-P communication in different condensate configurations. We find that E-P interactions are most consistent with experimental data when they occur on the surface of spherical condensates. Based on this finding, we propose a gene expression regulation model in which enhancers and promoters dynamically "kiss" on the condensate surface. We also show that our model can account for the phenomenon of gene expression bursting, as observed by single-molecule tracking. Our model provides a simple yet powerful framework for understanding enhancer-mediated gene regulation.