Genome-scale functional characterization of Drosophila developmental enhancers in vivo

Nature. 2014 Aug 7;512(7512):91-5. doi: 10.1038/nature13395. Epub 2014 Jun 1.

Abstract

Transcriptional enhancers are crucial regulators of gene expression and animal development and the characterization of their genomic organization, spatiotemporal activities and sequence properties is a key goal in modern biology. Here we characterize the in vivo activity of 7,705 Drosophila melanogaster enhancer candidates covering 13.5% of the non-coding non-repetitive genome throughout embryogenesis. 3,557 (46%) candidates are active, suggesting a high density with 50,000 to 100,000 developmental enhancers genome-wide. The vast majority of enhancers display specific spatial patterns that are highly dynamic during development. Most appear to regulate their neighbouring genes, suggesting that the cis-regulatory genome is organized locally into domains, which are supported by chromosomal domains, insulator binding and genome evolution. However, 12 to 21 per cent of enhancers appear to skip non-expressed neighbours and regulate a more distal gene. Finally, we computationally identify cis-regulatory motifs that are predictive and required for enhancer activity, as we validate experimentally. This work provides global insights into the organization of an animal regulatory genome and the make-up of enhancer sequences and confirms and generalizes principles from previous studies. All enhancer patterns are annotated manually with a controlled vocabulary and all results are available through a web interface (http://enhancers.starklab.org), including the raw images of all microscopy slides for manual inspection at arbitrary zoom levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics*
  • Embryonic Development / genetics*
  • Enhancer Elements, Genetic / genetics*
  • Gene Expression Regulation, Developmental / genetics*
  • Genome, Insect / genetics*
  • Internet
  • Nucleotide Motifs / genetics
  • Organ Specificity / genetics
  • Regulatory Sequences, Nucleic Acid / genetics
  • Reproducibility of Results
  • User-Computer Interface