Diverse Spatial Expression Patterns Emerge from Unified Kinetics of Transcriptional Bursting

Cell. 2018 Oct 18;175(3):835-847.e25. doi: 10.1016/j.cell.2018.09.056.

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.

Keywords: Bayesian inference; Drosophila gap genes; embryonic development; pattern formation; single-molecule imaging; telegraph model; transcriptional kinetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • DNA-Directed RNA Polymerases / metabolism
  • Drosophila melanogaster
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Regulation, Developmental*
  • Models, Theoretical
  • Promoter Regions, Genetic
  • Transcriptional Activation*

Substances

  • DNA-Directed RNA Polymerases