title: Shadow enhancers enable Hunchback bifunctionality in the Drosophila embryo.
abstract: 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.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
authors.forename: Max V
authors.initials: MV
authors.lastname: Staller
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Vincent
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
authors.forename: Meghan D J
authors.initials: MD
authors.lastname: Bragdon
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
authors.forename: Tara
authors.initials: T
authors.lastname: Lydiard-Martin
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
authors.forename: Zeba
authors.initials: Z
authors.lastname: Wunderlich
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
authors.forename: Javier
authors.initials: J
authors.lastname: Estrada
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115 angela_depace@hms.harvard.edu.
authors.forename: Angela H
authors.initials: AH
authors.lastname: DePace
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C061245:hb protein, Drosophila
keywords: Drosophila development; Hunchback; bifunctional transcription factor; computational model; enhancer