A dynamic kissing model for enhancer-promoter communication on the surface of transcriptional 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 result from liquid-liquid phase separation. However, the detailed kinetic mechanisms by which condensates may mediate enhancer-promoter contacts remain unclear. Here, we characterized enhancer-promoter communication in condensates using a self-avoiding polymer chain model under several possible spatial constraints. When the chain was confined to the spherical surface or interior, we discovered a distinct relationship between average end-to-end distance and contour length, as well as a distinct distribution of end-to-end distance. Experimental molecular tracking data showed strong preference in support of the spherical surface confinement hypothesis. Based on such observation, we proposed a novel enhancer-promoter communication model in which enhancers dynamically "kiss" promoters along the surface of transcriptional condensate. The theoretical results may guide future experiments, as researchers continue to elucidate the regulation dynamics of gene expression.