Genome-scale characterization of developmental enhancers in flies

Our genome-scale characterization of in vivo activities for 7705 enhancer candidates throughout Drosophila embryogenesis is published in Nature [1].

Developmental enhancers 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, including the raw images of all microscopy slides for manual inspection at arbitrary zoom levels.

[1] Kvon EZ, Kazmar T, Stampfel G*, Yáñez-Cuna JO*, Pagani M, Schernhuber K, Dickson BJ, Stark A. Genome-scale functional characterization of Drosophila developmental enhancers in vivo. Nature, 2014. Epub ahead of print. Pubmed 24896182.