Gene activity fully predicts transcriptional bursting dynamics

TL;DR

This study reveals that gene activity levels can fully predict transcriptional bursting dynamics, showing a fundamental relationship between ON/OFF periods across different conditions and species.

Contribution

It demonstrates that bursting parameters are intrinsically linked and governed by a unified mechanism, challenging the idea of independent regulation of burst size and frequency.

Findings

Gene activity predicts ON and OFF durations across conditions.

Low transcription correlates with longer OFF periods, high with longer ON periods.

Bursting dynamics are conserved across species and resilient to regulatory perturbations.

Abstract

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.