Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project

By Mark Gerstein, Z. Lu, Eric L. Van Nostrand, Chao Cheng, Bradley I. Arshinoff, Tao Liu, Kevin Y. Yip, R. Robilotto, Andreas Rechtsteiner, Kohta Ikegami and 121 more. Science, 2010

1,033 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. Extensive analysis of the Caenorhabditis elegans genome reveals regions highly occupied by multiple transcription factors. We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor–binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor–binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.

Subfields: Aging, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c3e64a24e22d9187d90f245c03613cddcdfe6947

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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”
Spatial reconstruction of single-cell gene expression (2015, methodology): “(2) We selected the 2n cells that had the lowest L2 distance (where n is the number of landmark genes), and were likely to be close in space to the bin.”
Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo (2015, background): “These regions have been termed highly occupied target (HOT) regions and have been identified in a wide variety of organisms (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).”
Regulation of nucleosome dynamics by histone modifications (2013, neutral): “Similar results have been observed in D. melanogaster 11 , Caenorhabditis elegans 86 , Arabidopsis thaliana 7 and in other human cell lines 102 .”
Roles for microRNAs in conferring robustness to biological processes. (2012, neutral): “Whole-genome bioinformatic analysis of worm and fly reveal transcription factors enriched in feedforward loops as well (Gerstein et al., 2010; modENCODE Consortium, 2010).”
Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics (2013, background): “19,290 genes were expressed in at least one tissue of this dataset, and of these, a total of 11,719 (137-2,626 per tissue) showed a tissue-specific pattern of expression as defined in (67).”
Pol III binding in six mammalian genomes shows high conservation among amino acid isotypes, despite divergence in tRNA gene usage (2011, neutral): “These factors can contribute in varying degrees towards controlling transcription, which greatly complicates our understanding of the relationship between binding location and regulator function 43-46 .”
ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia (2012, methodology): “For organisms with small genomes, the modENCODE Consortium has used both ChIP-chip and ChIP-seq, as modern arrays can provide high-resolution coverage of small genomes (Gerstein et al. 2010; Roy et al. 2010).”