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Cell Rep. 2014 Dec 24;9(6):2290-303. doi: 10.1016/j.celrep.2014.11.038. Epub 2014 Dec 18.

Mapping gene regulatory networks in Drosophila eye development by large-scale transcriptome perturbations and motif inference.

Author information

1
Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven 3000, Belgium.
2
Department of Electrical Engineering and Computer Science and GIGA-R, University of Liège, Liège 4000, Belgium.
3
Department of Molecular Biology and Genetics, Bogazici University, Istanbul 34342, Turkey.
4
Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven 3000, Belgium. Electronic address: stein.aerts@med.kuleuven.be.

Abstract

Genome control is operated by transcription factors (TFs) controlling their target genes by binding to promoters and enhancers. Conceptually, the interactions between TFs, their binding sites, and their functional targets are represented by gene regulatory networks (GRNs). Deciphering in vivo GRNs underlying organ development in an unbiased genome-wide setting involves identifying both functional TF-gene interactions and physical TF-DNA interactions. To reverse engineer the GRNs of eye development in Drosophila, we performed RNA-seq across 72 genetic perturbations and sorted cell types and inferred a coexpression network. Next, we derived direct TF-DNA interactions using computational motif inference, ultimately connecting 241 TFs to 5,632 direct target genes through 24,926 enhancers. Using this network, we found network motifs, cis-regulatory codes, and regulators of eye development. We validate the predicted target regions of Grainyhead by ChIP-seq and identify this factor as a general cofactor in the eye network, being bound to thousands of nucleosome-free regions.

PMID:
25533349
DOI:
10.1016/j.celrep.2014.11.038
[Indexed for MEDLINE]
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