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    Date Issued2007 (1)2006 (1)AuthorGrove, Christian A. (2)Hope, Ian A. (2)Reece-Hoyes, John S. (2)
    Shingles, Jane (2)
    Walhout, Albertha J. M. (2)View MoreUMass Chan AffiliationProgram in Gene Function and Expression (2)Program in Molecular Medicine (2)Graduate School of Biomedical Sciences (1)Document TypeJournal Article (2)KeywordLife Sciences (2)Medicine and Health Sciences (2)Animals; Caenorhabditis elegans; Computational Biology; Databases, Genetic; Dimerization; Genes, Helminth; Genes, Regulator; Helminth Proteins; Humans; Open Reading Frames; Promoter Regions (Genetics); Protein Interaction Mapping; Protein Structure, Tertiary; RNA Splicing; Transcription Factors; *Transcription, Genetic (1)Animals; Caenorhabditis; Caenorhabditis elegans; *Gene Duplication; *Gene Expression Regulation; Genes, Reporter; Genetic Techniques; Genomics; Green Fluorescent Proteins; Phylogeny; *Promoter Regions (Genetics); Species Specificity; Transcription Factors (1)View MoreJournalBMC genomics (1)Genome biology (1)

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    Insight into transcription factor gene duplication from Caenorhabditis elegans Promoterome-driven expression patterns

    Reece-Hoyes, John S.; Shingles, Jane; Dupuy, Denis; Grove, Christian A.; Walhout, Albertha J. M.; Vidal, Marc; Hope, Ian A. (2007-01-25)
    BACKGROUND: The C. elegans Promoterome is a powerful resource for revealing the regulatory mechanisms by which transcription is controlled pan-genomically. Transcription factors will form the core of any systems biology model of genome control and therefore the promoter activity of Promoterome inserts for C. elegans transcription factor genes was examined, in vivo, with a reporter gene approach. RESULTS: Transgenic C. elegans strains were generated for 366 transcription factor promoter/gfp reporter gene fusions. GFP distributions were determined, and then summarized with reference to developmental stage and cell type. Reliability of these data was demonstrated by comparison to previously described gene product distributions. A detailed consideration of the results for one C. elegans transcription factor gene family, the Six family, comprising ceh-32, ceh-33, ceh-34 and unc-39 illustrates the value of these analyses. The high proportion of Promoterome reporter fusions that drove GFP expression, compared to previous studies, led to the hypothesis that transcription factor genes might be involved in local gene duplication events less frequently than other genes. Comparison of transcription factor genes of C. elegans and Caenorhabditis briggsae was therefore carried out and revealed very few examples of functional gene duplication since the divergence of these species for most, but not all, transcription factor gene families. CONCLUSION: Examining reporter expression patterns for hundreds of promoters informs, and thereby improves, interpretation of this data type. Genes encoding transcription factors involved in intrinsic developmental control processes appear acutely sensitive to changes in gene dosage through local gene duplication, on an evolutionary time scale.
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    A compendium of Caenorhabditis elegans regulatory transcription factors: a resource for mapping transcription regulatory networks

    Reece-Hoyes, John S.; Deplancke, Bart; Shingles, Jane; Grove, Christian A.; Hope, Ian A.; Walhout, Albertha J. M. (2006-01-20)
    BACKGROUND: Transcription regulatory networks are composed of interactions between transcription factors and their target genes. Whereas unicellular networks have been studied extensively, metazoan transcription regulatory networks remain largely unexplored. Caenorhabditis elegans provides a powerful model to study such metazoan networks because its genome is completely sequenced and many functional genomic tools are available. While C. elegans gene predictions have undergone continuous refinement, this is not true for the annotation of functional transcription factors. The comprehensive identification of transcription factors is essential for the systematic mapping of transcription regulatory networks because it enables the creation of physical transcription factor resources that can be used in assays to map interactions between transcription factors and their target genes. RESULTS: By computational searches and extensive manual curation, we have identified a compendium of 934 transcription factor genes (referred to as wTF2.0). We find that manual curation drastically reduces the number of both false positive and false negative transcription factor predictions. We discuss how transcription factor splice variants and dimer formation may affect the total number of functional transcription factors. In contrast to mouse transcription factor genes, we find that C. elegans transcription factor genes do not undergo significantly more splicing than other genes. This difference may contribute to differences in organism complexity. We identify candidate redundant worm transcription factor genes and orthologous worm and human transcription factor pairs. Finally, we discuss how wTF2.0 can be used together with physical transcription factor clone resources to facilitate the systematic mapping of C. elegans transcription regulatory networks. CONCLUSION: wTF2.0 provides a starting point to decipher the transcription regulatory networks that control metazoan development and function.
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