PT  - JOURNAL ARTICLE
AU  - Caroline Hoppe
AU  - Jonathan Bowles
AU  - Thomas G. Minchington
AU  - Catherine Sutcliffe
AU  - Priyanka Upadhyai
AU  - Magnus Rattray
AU  - Hilary L. Ashe
TI  - Modulation of promoter occupancy dictates the transcriptional response to graded BMP signalling levels in the <em>Drosophila</em> embryo
AID  - 10.1101/837179
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 837179
4099  - http://biorxiv.org/content/early/2019/11/25/837179.short
4100  - http://biorxiv.org/content/early/2019/11/25/837179.full
AB  - Morphogen gradients specify cell fates during development, with a classic example being the BMP gradient’s conserved role in embryonic dorsal-ventral axis patterning. Here we use quantitative imaging and computational modelling to determine how the BMP gradient is interpreted at single-cell resolution in the Drosophila embryo. We show that BMP signalling levels are decoded by modulating promoter occupancy, the time the promoter is active, predominantly through regulating the promoter activation rate. As a result, graded mRNA numbers are detected for BMP target genes in cells across their expression domains. Introducing a heterologous promoter into a BMP target gene changes burst amplitude but not promoter occupancy suggesting that, while the promoter sequence controls amplitude, occupancy depends on the amount of BMP signal decoded by the enhancer. We provide evidence that graded mRNA output is a general feature of morphogen gradient interpretation and discuss how this can impact on cell fate decisions.