title: Whole-genome analysis of temporal gene expression during foregut development.
abstract: We have investigated the cis-regulatory network that mediates temporal gene expression during organogenesis. Previous studies demonstrated that the organ selector gene pha-4/FoxA is critical to establish the onset of transcription of Caenorhabditis elegans foregut (pharynx) genes. Here, we discover additional cis-regulatory elements that function in combination with PHA-4. We use a computational approach to identify candidate cis-regulatory sites for genes activated either early or late during pharyngeal development. Analysis of natural or synthetic promoters reveals that six of these sites function in vivo. The newly discovered temporal elements, together with predicted PHA-4 sites, account for the onset of expression of roughly half of the pharyngeal genes examined. Moreover, combinations of temporal elements and PHA-4 sites can be used in genome-wide searches to predict pharyngeal genes, with more than 85% accuracy for their onset of expression. These findings suggest a regulatory code for temporal gene expression during foregut development and provide a means to predict gene expression patterns based solely on genomic sequence.
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Jeb
authors.initials: J
authors.lastname: Gaudet
authors.forename: Srikanth
authors.initials: S
authors.lastname: Muttumu
authors.forename: Michael
authors.initials: M
authors.lastname: Horner
authors.forename: Susan E
authors.initials: SE
authors.lastname: Mango
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D003062:Codon; D019295:Computational Biology; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D016678:Genome; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007422:Intestines / Q000196:embryology*; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050436:Regulatory Elements, Transcriptional; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D019076:Transgenes
chemical_list: D029742:Caenorhabditis elegans Proteins; D003062:Codon; C113277:Pha-4 protein, C elegans; D015534:Trans-Activators; D049452:Green Fluorescent Proteins