TY - JOUR
T1 - Shadow enhancers enable hunchback bifunctionality in the Drosophila embryo
AU - Staller, Max V.
AU - Vincent, Ben J.
AU - Bragdon, Meghan D.J.
AU - Lydiard-Martin, Tara
AU - Wunderlich, Zeba
AU - Estrada, Javier
AU - DePace, Angela H.
PY - 2015/1/20
Y1 - 2015/1/20
N2 - 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.
AB - 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.
KW - Bifunctional transcription factor
KW - Computational model
KW - Drosophila development
KW - Enhancer
KW - Hunchback
UR - http://www.scopus.com/inward/record.url?scp=84921534874&partnerID=8YFLogxK
U2 - 10.1073/pnas.1413877112
DO - 10.1073/pnas.1413877112
M3 - Article
C2 - 25564665
AN - SCOPUS:84921534874
SN - 0027-8424
VL - 112
SP - 785
EP - 790
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
ER -