Kinetic model of E-P condensates dynamics reveals transcriptional speed, noise, and energy trade-offs.

Abstract

Gene regulation emerges from the interplay between chromatin architecture and the molecular interactions that connect enhancers to promoters. To study how these interactions shape transcriptional dynamics, we developed a kinetic model that incorporates multivalent enhancer-promoter binding, transcription factor competition, steric constraints, and chromatin accessibility. The model shows that competition among regulatory factors can generate bistable promoter states at the expense of increased transcriptional noise, revealing a direct relationship between bistability and noise levels. It further predicts that promoter response times are fastest in parameter regimes where bistability appears, suggesting that regulatory dynamics supporting two promoter states may intrinsically enable rapid activation. Extending this analysis, we find that intermediate chromatin accessibility and competition between activators and repressors both promote bistable enhancer-bound promoter clusters and fast switching at the cost of higher noise, whereas very high or low accessibility and noncompetitive transcription factors result in monostable expression states. The model also offers a quantitative framework to compare the energetic costs of different regulatory strategies, indicating that, under energy constraints, cells may favor adjusting transcription factor concentrations rather than altering chromatin accessibility, thereby linking energy expenditure to regulatory flexibility and robustness.