Mapping Gene Regulatory Networks in Drosophila Eye Development by Large-Scale Transcriptome Perturbations and Motif Inference

• Published in: Cell reports (Cambridge) Vol. 9; no. 6; pp. 2290 - 2303
• Main Authors: Potier, Delphine, Davie, Kristofer, Hulselmans, Gert, Naval Sanchez, Marina, Haagen, Lotte, Huynh-Thu, Vân Anh, Koldere, Duygu, Celik, Arzu, Geurts, Pierre, Christiaens, Valerie, Aerts, Stein
• Format: Journal Article Web Resource
• Language: English
• Published: United States Elsevier Inc 24-12-2014; Elsevier
• Subjects: Animals; Compound Eye, Arthropod - growth & development; Compound Eye, Arthropod - metabolism; Drosophila - genetics; Drosophila - growth & development; Drosophila - metabolism; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Genetics & genetic processes; Génétique & processus génétiques; Life sciences; Nucleotide Motifs; Sciences du vivant; Transcriptome
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2014.11.038

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.
[Display omitted]
•Developmental GRNs can be reverse engineered by RNA-seq and motif inference•More than 200 TFs and their target genes are added to the Drosophila eye network•Motifs of TFs are enriched in enhancers of their coexpressed genes•Grainyhead targets are validated by ChIP-seq and correlate with chromatin opening
Potier et al. predict the gene regulatory network of Drosophila eye development by combining network inference on 72 perturbation RNA-seq experiments with motif prediction, adding many players to the eye network. ChIP-seq confirms the predicted widespread binding of Grainyhead and its correlation with open chromatin in the eye disc.