Gene Activity as the Predictive Indicator for Transcriptional Bursting Dynamics

Transcription commonly occurs in bursts, with alternating productive (ON) and quiescent (OFF) periods, governing mRNA production rates. Yet, how transcription is regulated through bursting dynamics remains unresolved. In this study, we conduct real-time measurements of endogenous transcriptional bursting with single-mRNA sensitivity. Leveraging the diverse transcriptional activities in early fly embryos, we uncover stringent relationships between bursting parameters. Specifically, we find that the durations of ON and OFF periods are linked. Regardless of the developmental stage or body-axis position, gene activity levels predict the average ON and OFF periods of individual alleles. Lowly transcribing alleles predominantly modulate OFF durations (burst frequency), while highly transcribing alleles primarily tune ON durations (burst size). Importantly, these relationships persist even under perturbation of cis-regulatory elements or trans-factors. This suggests a novel mechanistic constraint governing bursting dynamics rather than a modular control of distinct parameters by distinct regulatory processes. Our study provides a foundation for future investigations into the molecular mechanisms underpinning spatiotemporal transcriptional control.