Enhancer additivity and non-additivity are determined by enhancer strength in the Drosophila embryo.

TitleEnhancer additivity and non-additivity are determined by enhancer strength in the Drosophila embryo.
Publication TypeJournal Article
Year of Publication2015
AuthorsBothma, JP, Garcia, HG, Ng, S, Perry, MW, Gregor, T, Levine, M
JournalElife
Volume4
Date Published2015 Aug 12
ISSN2050-084X
KeywordsAnimals, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Embryonic Development, Enhancer Elements, Genetic, Evaluation Studies as Topic, Gene Expression Regulation, Developmental, Optical Imaging, Promoter Regions, Genetic, Repressor Proteins, Snail Family Transcription Factors, Transcription Factors
Abstract

<p>Metazoan genes are embedded in a rich milieu of regulatory information that often includes multiple enhancers possessing overlapping activities. In this study, we employ quantitative live imaging methods to assess the function of pairs of primary and shadow enhancers in the regulation of key patterning genes-knirps, hunchback, and snail-in developing Drosophila embryos. The knirps enhancers exhibit additive, sometimes even super-additive activities, consistent with classical gene fusion studies. In contrast, the hunchback enhancers function sub-additively in anterior regions containing saturating levels of the Bicoid activator, but function additively in regions where there are diminishing levels of the Bicoid gradient. Strikingly sub-additive behavior is also observed for snail, whereby removal of the proximal enhancer causes a significant increase in gene expression. Quantitative modeling of enhancer-promoter interactions suggests that weakly active enhancers function additively while strong enhancers behave sub-additively due to competition with the target promoter. </p>

DOI10.7554/eLife.07956
Alternate JournalElife
PubMed ID26267217
PubMed Central IDPMC4532966
Grant ListR01 GM097275 / GM / NIGMS NIH HHS / United States
GM071508 / GM / NIGMS NIH HHS / United States
GM097275 / GM / NIGMS NIH HHS / United States
GM34431 / GM / NIGMS NIH HHS / United States