Molecular competition can shape enhancer activity in the Drosophila embryo

Rachel Waymack; Mario Gad; Zeba Wunderlich

doi:10.1016/j.isci.2021.103034

Molecular competition can shape enhancer activity in the Drosophila embryo

iScience. 2021 Aug 25;24(9):103034. doi: 10.1016/j.isci.2021.103034. eCollection 2021 Sep 24.

Authors

Rachel Waymack¹, Mario Gad¹, Zeba Wunderlich^{1

2

3}

Affiliations

¹ Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA.
² Department of Biology, Boston University, 610 Commonwealth Ave., Boston, MA 02215, USA.
³ Biological Design Center, Boston University, 610 Commonwealth Avenue, Boston, MA 02215, USA.

Abstract

Transgenic reporters allow the measurement of regulatory DNA activity in vivo and consequently have long been useful tools for studying enhancers. Despite their utility, few studies have investigated the effects these reporters may have on the expression of other genes. Understanding these effects is required to accurately interpret reporter data and characterize gene regulatory mechanisms. By measuring the expression of Kruppel (Kr) enhancer reporters in live Drosophila embryos, we find reporters inhibit one another's expression and that of a nearby endogenous gene. Using synthetic transcription factor (TF) binding site arrays, we present evidence that competition for TFs is partially responsible for the observed transcriptional inhibition. We develop a simple thermodynamic model that predicts competition of the measured magnitude specifically when TF binding is restricted to distinct nuclear subregions. Our findings underline an unexpected role of the non-homogenous nature of the nucleus in regulating gene expression.

Keywords: Biological sciences; Cell biology; Developmental biology; Mathematical biosciences; Molecular biology; Molecular interaction.

Grants and funding

R01 HD095246/HD/NICHD NIH HHS/United States