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Mapping gene regulatory networks in Drosophila eye development by large-scale transcriptome perturbations and motif inference [ChIP-Seq]

ABSTRACT: Genome control is operated by transcription factors (TF) 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 (GRN). 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 GRN of eye development in Drosophila, we performed RNA-seq across 72 genetic perturbations and sorted cell types, and inferred a co-expression network. Next, we derived direct TF-DNA interactions using computational motif inference, ultimately connecting 241 TFs to 5632 direct target genes through 24926 enhancers. Using this network we found network motifs, cis-regulatory codes, and new regulators of eye development. We validate the predicted target regions of Grainyhead by ChIP-seq and identify this factor as a general co-factor in the eye network, being bound to thousands of nucleosome-free regions.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE62557 | GEO | 2014/12/01

SECONDARY ACCESSION(S): PRJNA264410

REPOSITORIES: GEO

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Project description:Understanding the regulatory genome remains a significant challenge. Annotation of regulatory elements and identification of the transcription factors (TFs) targeting these elements are key steps in understanding how a given cell interprets its genetic blueprint. One goal of the modENCODE (model organism Encyclopedia of DNA Elements) project is to survey a diverse sampling of TFs, both DNA-binding and non-DNA binding factors, to provide a framework for the subsequent study of the mechanisms by which transcriptional regulators target the genome. Here we provide an updated map of the Drosophila melanogaster regulatory genome based on the location of 84 TFs at various stages of development. This regulatory map reveals a variety of genomic targeting patterns, including factors with strong preferences toward proximal promoter binding, factors that target intergenic and intronic DNA, and factors with distinct chromatin state preferences. The data also suggest the existence of a partially self-contained Polycomb regulatory network, and highlight the importance of Trithorax-like (Trl) in maintaining hotspots of DNA binding throughout development. Furthermore, the data identify over 5,800 instances in which TFs target DNA regions with demonstrated enhancer activity. Regions of high TF co-occupancy are more likely to be associated with open enhancers used across cell types, while lower TF occupancy regions are associated with complex enhancers that are also regulated at the epigenetic level. A putative regulatory network generated based on these 84 regulators reveals hundreds of co-binding events, thousands of potential regulatory interactions, and distinct regulatory strategies at developmental and housekeeping genes. These data serve as a resource for the research community in the continued effort to dissect transcriptional regulatory mechanisms directing Drosophila development. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf This is a dataset generated by the Drosophila Regulatory Elements modENCODE Project led by Kevin P. White at the University of Chicago.

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Mapping gene regulatory networks in Drosophila eye development by large-scale transcriptome perturbations and motif inference [ChIP-Seq]

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