Shadow enhancers enable Hunchback bifunctionality in the Drosophila embryo.
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.
['Staller|Max V|MV|', 'Vincent|Ben J|BJ|', 'Bragdon|Meghan D J|MD|', 'Lydiard-Martin|Tara|T|', 'Wunderlich|Zeba|Z|', 'Estrada|Javier|J|', 'DePace|Angela H|AH|']
D000818:Animals D004268:DNA-Binding Proteins D004330:Drosophila D029721:Drosophila Proteins D004742:Enhancer Elements, Genetic D014157:Transcription Factors
enhancer Hunchback bifunctional transcription factor computational model Drosophila development