Diverse Spatial Expression Patterns Emerge from Unified Kinetics of Transcriptional Bursting

Benjamin Zoller, Shawn C. Little, Thomas Gregor

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

How transcriptional bursting relates to gene regulation is a central question that has persisted for more than a decade. Here, we measure nascent transcriptional activity in early Drosophila embryos and characterize the variability in absolute activity levels across expression boundaries. We demonstrate that boundary formation follows a common transcription principle: a single control parameter determines the distribution of transcriptional activity, regardless of gene identity, boundary position, or enhancer-promoter architecture. We infer the underlying bursting kinetics and identify the key regulatory parameter as the fraction of time a gene is in a transcriptionally active state. Unexpectedly, both the rate of polymerase initiation and the switching rates are tightly constrained across all expression levels, predicting synchronous patterning outcomes at all positions in the embryo. These results point to a shared simplicity underlying the apparently complex transcriptional processes of early embryonic patterning and indicate a path to general rules in transcriptional regulation. Multiple gene expression boundaries in a developing embryo arise from the same strategy of modulated transcriptional bursting rates.

Original languageEnglish (US)
Pages (from-to)835-847.e25
JournalCell
Volume175
Issue number3
DOIs
StatePublished - Oct 18 2018

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology

Keywords

  • Bayesian inference
  • Drosophila gap genes
  • embryonic development
  • pattern formation
  • single-molecule imaging
  • telegraph model
  • transcriptional kinetics

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