  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. Here,
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 individual alleles' average ON and OFF periods. Lowly
transcribing alleles predominantly modulate OFF periods (burst frequency),
while highly transcribing alleles primarily tune ON periods (burst size). These
relationships persist even under perturbations of cis-regulatory elements or
trans-factors and account for bursting dynamics measured in other species. Our
results suggest a novel mechanistic constraint governing bursting dynamics
rather than a modular control of distinct parameters by distinct regulatory
processes.
