Signal Integration by Shadow Enhancers and Enhancer Duplications Varies across the Drosophila Embryo

Abstract

Transcription of developmental genes is controlled by multiple enhancers. Frequently, more than one enhancer can activate transcription from the same promoter in the same cells. How is regulatory information from multiple enhancers combined to determine the overall expression output? We measure nascent transcription driven by a pair of shadow enhancers, each enhancer of the pair separately, and each duplicated, using live imaging in Drosophila embryos. This set of constructs allows us to quantify the input-output function describing signal integration by two enhancers. We show that signal integration performed by these shadow enhancers and duplications varies across the expression pattern, implying that how their activities are combined depends on the transcriptional regulators bound to the enhancers in different parts of the embryo. Characterizing signal integration by multiple enhancers is a critical step in developing conceptual and computational models of gene expression at the locus level, where multiple enhancers control transcription together. Scholes et al. examine how shadow enhancers and enhancer duplications drive expression from a single promoter. They show that “signal integration” varies across the expression pattern, implying that how enhancers’ activities combine depends on the transcriptional regulators they bind in different parts of the embryo.