Shadow enhancers enable hunchback bifunctionality in the Drosophila embryo

Max V. Staller, Ben J. Vincent, Meghan D.J. Bragdon, Tara Lydiard-Martin, Zeba Wunderlich, Javier Estrada, Angela H. DePace

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


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 37 enhancer (eve37) in Drosophila blastoderm embryos. We measured and modeled eve expression at cellular resolution under multiple genetic perturbations and found that the eve37 enhancer could not explain endogenous eve stripe 7 behavior. Instead, we found that eve stripe 7 is controlled by two enhancers: the canonical eve37 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 eve27 enhancer and represses the eve37 enhancer. These two "shadow enhancers" use different regulatory logic to create the same pattern.

Original languageEnglish
Pages (from-to)785-790
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
StatePublished - Jan 20 2015


  • Bifunctional transcription factor
  • Computational model
  • Drosophila development
  • Enhancer
  • Hunchback


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