Hormone-responsive enhancer-activity maps reveal predictive motifs, indirect repression, and targeting of closed chromatin

Mol Cell. 2014 Apr 10;54(1):180-192. doi: 10.1016/j.molcel.2014.02.026. Epub 2014 Mar 27.


Steroid hormones act as important developmental switches, and their nuclear receptors regulate many genes. However, few hormone-dependent enhancers have been characterized, and important aspects of their sequence architecture, cell-type-specific activating and repressing functions, or the regulatory roles of their chromatin structure have remained unclear. We used STARR-seq, a recently developed enhancer-screening assay, and ecdysone signaling in two different Drosophila cell types to derive genome-wide hormone-dependent enhancer-activity maps. We demonstrate that enhancer activation depends on cis-regulatory motif combinations that differ between cell types and can predict cell-type-specific ecdysone targeting. Activated enhancers are often not accessible prior to induction. Enhancer repression following hormone treatment seems independent of receptor motifs and receptor binding to the enhancer, as we show using ChIP-seq, but appears to rely on motifs for other factors, including Eip74. Our strategy is applicable to study signal-dependent enhancers for different pathways and across organisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chromatin Assembly and Disassembly / drug effects*
  • Computational Biology
  • Databases, Genetic
  • Drosophila melanogaster / drug effects*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Ecdysone / pharmacology*
  • Enhancer Elements, Genetic / drug effects*
  • Epigenetic Repression / drug effects*
  • Female
  • Gene Expression Regulation / drug effects
  • High-Throughput Nucleotide Sequencing
  • Nucleotide Motifs / drug effects*
  • Ovary / drug effects*
  • Ovary / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Support Vector Machine
  • Transcriptional Activation / drug effects
  • Transfection


  • Ecdysone