Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE

By Sushmita Roy, Jason Ernst, Peter V. Kharchenko, Pouya Kheradpour, N. Negre, M. Eaton, J. Landolin, C. Bristow, Lijia Ma, Michael F. Lin and 86 more. Science, 2010

820 citations recorded by the source corpus.

From Genome to Regulatory Networks For biologists, having a genome in hand is only the beginning—much more investigation is still needed to characterize how the genome is used to help to produce a functional organism (see the Perspective by Blaxter). In this vein, Gerstein et al. (p. 1775) summarize for the Caenorhabditis elegans genome, and The modENCODE Consortium (p. 1787) summarize for the Drosophila melanogaster genome, full transcriptome analyses over developmental stages, genome-wide identification of transcription factor binding sites, and high-resolution maps of chromatin organization. Both studies identified regions of the nematode and fly genomes that show highly occupied targets (or HOT) regions where DNA was bound by more than 15 of the transcription factors analyzed and the expression of related genes were characterized. Overall, the studies provide insights into the organization, structure, and function of the two genomes and provide basic information needed to guide and correlate both focused and genome-wide studies. The Drosophila modENCODE project demonstrates the functional regulatory network of flies. To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.

Subfields: Aging, Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ff518d528a9538a20843d1f6f494be0b5bb465a5

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Citations in the corpus

JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles (2013, methodology): “We compiled published sequence-specific DNA binding TF chromatin immunoprecipitation (ChIP)-seq data collections into the PAZAR database (11,12) along with TF ChIP-seq datasets from the ENCODE (13–15) and modENCODE (16,17) consortia for Homo sapiens, Mus musculus, Drosophila melanogaster and Caenorh”
Temporal Coordination of Gene Networks by Zelda in the Early Drosophila Embryo (2011, methodology): “(E) Hotspots (3163 with at least eight factors bound) were divided into windows containing 100 hotspots each, and ranked from high to low according to hotspot scores [5] (X-axis, 1 = highest ranking score).”
Chromatin-state discovery and genome annotation with ChromHMM (2017, methodology): “Large consortium projects, including ENCODE 10 , Roadmap Epigenomics 3 , Blueprint 15 , CEEHRC 16 , Mouse ENCODE 17 , and Drosophila modENCODE 18 , have used ChromHMM as a basis for their analyses.”
Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo (2015, background): “…are bound by a large number of different transcription factors, have been identified in multiple organisms, including worms, flies, and humans (Moorman et al. 2006; The ENCODE Project Consortium 2007; Li et al. 2008; MacArthur et al. 2009; Gerstein et al. 2010; Roy et al. 2010; Negre et al. 2011).”