학술논문

Shadow enhancers enable Hunchback bifunctionality in the Drosophila embryo
Document Type
article
Source
Proceedings of the National Academy of Sciences of the United States of America. 112(3)
Subject
Biological Sciences
Genetics
Underpinning research
1.1 Normal biological development and functioning
Generic health relevance
Animals
DNA-Binding Proteins
Drosophila
Drosophila Proteins
Enhancer Elements
Genetic
Transcription Factors
enhancer
computational model
bifunctional transcription factor
Drosophila development
Hunchback
Language
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.