Power-law behavior of transcriptional bursting regulated by enhancer-promoter communication.

ABSTRACT

Revealing how transcriptional bursting kinetics are genomically encoded is challenging because genome structures are stochastic at the organization level and are suggestively linked to gene transcription. To address this challenge, we develop a generic theoretical framework that integrates chromatin dynamics, enhancer-promoter (E-P) communication, and gene-state switching to study transcriptional bursting. The theory predicts that power law can be a general rule to quantitatively describe bursting modulations by E-P spatial communication. Specifically, burst frequency and burst size are up-regulated by E-P communication strength, following power laws with positive exponents. Analysis of the scaling exponents further reveals that burst frequency is preferentially regulated. Bursting kinetics are down-regulated by E-P genomic distance with negative power-law exponents, and this negative modulation desensitizes at large distances. The mutual information between burst frequency (or burst size) and E-P spatial distance further reveals essential characteristics of the information transfer from E-P communication to transcriptional bursting kinetics. These findings, which are in agreement with experimental observations, not only reveal fundamental principles of E-P communication in transcriptional bursting but also are essential for understanding cellular decision-making.