title: Mapping gene regulatory networks in Drosophila eye development by large-scale transcriptome perturbations and motif inference.
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.
authors.affiliation: Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven 3000, Belgium.
authors.forename: Delphine
authors.initials: D
authors.lastname: Potier
authors.affiliation: Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven 3000, Belgium.
authors.forename: Kristofer
authors.initials: K
authors.lastname: Davie
authors.affiliation: Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven 3000, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Hulselmans
authors.affiliation: Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven 3000, Belgium.
authors.forename: Marina
authors.initials: M
authors.lastname: Naval Sanchez
authors.affiliation: Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven 3000, Belgium.
authors.forename: Lotte
authors.initials: L
authors.lastname: Haagen
authors.affiliation: Department of Electrical Engineering and Computer Science and GIGA-R, University of Liège, Liège 4000, Belgium.
authors.forename: Vân Anh
authors.initials: VA
authors.lastname: Huynh-Thu
authors.affiliation: Department of Molecular Biology and Genetics, Bogazici University, Istanbul 34342, Turkey.
authors.forename: Duygu
authors.initials: D
authors.lastname: Koldere
authors.affiliation: Department of Molecular Biology and Genetics, Bogazici University, Istanbul 34342, Turkey.
authors.forename: Arzu
authors.initials: A
authors.lastname: Celik
authors.affiliation: Department of Electrical Engineering and Computer Science and GIGA-R, University of Liège, Liège 4000, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Geurts
authors.affiliation: Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven 3000, Belgium.
authors.forename: Valerie
authors.initials: V
authors.lastname: Christiaens
authors.affiliation: Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven 3000, Belgium. Electronic address: stein.aerts@med.kuleuven.be.
authors.forename: Stein
authors.initials: S
authors.lastname: Aerts
mesh_terms: D000818:Animals; D054910:Compound Eye, Arthropod / Q000254:growth & development / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D059372:Nucleotide Motifs; D059467:Transcriptome