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

Genome-scale functional characterization of Drosophila developmental enhancers in vivo.

Author information

1
1] Research Institute of Molecular Pathology (IMP), Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria [2] Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147, USA (B.J.D.); Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA (E.Z.K.).
2
Research Institute of Molecular Pathology (IMP), Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria.
3
1] Research Institute of Molecular Pathology (IMP), Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria [2].

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.

PMID:
24896182
DOI:
10.1038/nature13395
[Indexed for MEDLINE]

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