Shadow enhancers enable Hunchback bifunctionality in the Drosophila embryo

Proc Natl Acad Sci U S A. 2015 Jan 20;112(3):785-90. doi: 10.1073/pnas.1413877112. Epub 2015 Jan 6.

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.

Keywords: Drosophila development; Hunchback; bifunctional transcription factor; computational model; enhancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Drosophila / embryology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Enhancer Elements, Genetic*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Transcription Factors
  • hb protein, Drosophila