Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo

Caroline Hoppe, Jonathan R. Bowles, Thomas G. Minchington, Catherine Sutcliffe, Priyanka Upadhyai, Magnus Rattray, Hilary L. Ashe

Research output: Contribution to journalArticlepeer-review

Abstract

Morphogen gradients specify cell fates during development, with a classic example being the bone morphogenetic protein (BMP) gradient’s conserved role in embryonic dorsal-ventral axis patterning. Here, we elucidate how the BMP gradient is interpreted in the Drosophila embryo by combining live imaging with computational modeling to infer transcriptional burst parameters at single-cell resolution. By comparing burst kinetics in cells receiving different levels of BMP signaling, we show that BMP signaling controls burst frequency by regulating the promoter activation rate. We provide evidence that the promoter activation rate is influenced by both enhancer and promoter sequences, whereas Pol II loading rate is primarily modulated by the enhancer. Consistent with BMP-dependent regulation of burst frequency, the numbers of BMP target gene transcripts per cell are graded across their expression domains. We suggest that graded mRNA output is a general feature of morphogen gradient interpretation and discuss how this can impact on cell-fate decisions.
Original languageEnglish
Pages (from-to)727-741.e7
JournalDevelopmental cell
Volume54
Issue number6
DOIs
Publication statusPublished - 5 Aug 2020

Keywords

  • BMP signaling
  • Dpp
  • Drosophila embryo
  • MS2
  • burst frequency
  • bursting
  • enhancer
  • live imaging
  • promoter
  • smFISH
  • transcription kinetics

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