RT Journal Article
SR Electronic
T1 Shadow enhancers enable Hunchback bifunctionality in the Drosophila embryo
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 007922
DO 10.1101/007922
A1 Max V. Staller
A1 Ben J. Vincent
A1 Meghan D.J. Bragdon
A1 Tara Lydiard-Martin Zeba Wunderlich
A1 Javier Estrada
A1 Angela H. DePace
YR 2015
UL http://biorxiv.org/content/early/2015/01/03/007922.abstract
AB Hunchback (Hb) is a bifunctional transcription factor that activates and represses distinct enhancers. Here, we investigate the hypothesis that Hb can activate and repress the same enhancer. Computational models predicted that Hb bifunctionally regulates the even-skipped (eve) stripe 3+7 enhancer (eve3+7) in Drosophila blastoderm embryos. We measured and modeled eve expression at cellular resolution under multiple genetic perturbations and found that the eve3+7 enhancer could not explain endogenous eve stripe 7 behavior. Instead, we found that eve stripe 7 is controlled by two enhancers: the canonical eve3+7 and a sequence encompassing the minimal eve stripe 2 enhancer (eve2+7). Hb bifunctionally regulates eve stripe 7, but it executes these two activities on different pieces of regulatory DNA–it activates the eve2+7 enhancer and represses the eve3+7 enhancer. These two “shadow enhancers” use different regulatory logic to create the same pattern.Significance statement Enhancers are regions of regulatory DNA that control gene expression and cell fate decisions during development. Enhancers compute the expression pattern of their target gene by reading the concentrations of input regulatory proteins. Many developmental genes contain multiple enhancers that control the same output pattern, but it is unclear if these enhancers all compute the pattern in the same way. We use measurements in single cells and computational models in Drosophila embryos to demonstrate that two enhancers that encode the same gene expression pattern compute differently: the same regulatory protein represses one enhancer and activates the other. Pairs of enhancers that output the same pattern by performing different computations may impart special properties to developmental systems.