101 / 2024-10-24 12:11:34

A dynamic kissing model for enhancer-promoter communication on the surface of transcriptional condensate

enhancer-promoter contact,condensate

ABSTRACT

Enhancers are key DNA elements that regulate gene transcription by activating promoters in eukaryotes. Many potential mechanistic models have been proposed to account for enhancer-promoter communication, including the formation of the condensed enhancer-promoter clusterings that may be caused by liquid-liquid phase separation. However, the detailed kinetic mechanism of how condensates may mediate enhancer-promoter contacts remains unclear. Here, we proposed a polymer physics-based model on condensates-mediated enhancerpromoter communication. We found that the model-derived distribution of end-to-end distance at a given contour length matched the experimental molecular tracking data most, when enhancer-promoter contacts were constrained to the spherical surface of condensates. Based on such observation, we further proposed a novel gene expression regulation model based on dynamic enhancer-promoter communication on the surface of transcriptional condensate. We showed that the dynamic kissing model well explained the pattern of gene expression bursting at single-molecular level.