title: Co-expression of the transcription factors CEH-14 and TTX-1 regulates AFD neuron-specific genes gcy-8 and gcy-18 in C. elegans.
abstract: A wide variety of cells are generated by the expression of characteristic sets of genes, primarily those regulated by cell-specific transcription. To elucidate the mechanism regulating cell-specific gene expression in a highly specialized cell, AFD thermosensory neuron in Caenorhabditis elegans, we analyzed the promoter sequences of guanylyl cyclase genes, gcy-8 and gcy-18, exclusively expressed in AFD. In this study, we showed that AFD-specific expression of gcy-8 and gcy-18 requires the co-expression of homeodomain proteins, CEH-14/LHX3 and TTX-1/OTX1. We observed that mutation of ttx-1 or ceh-14 caused a reduction in the expression of gcy-8 and gcy-18 and that the expression was completely lost in double mutants. This synergy effect was also observed with other AFD marker genes, such as ntc-1, nlp-21and cng-3. Electrophoretic mobility shift assays revealed direct interaction of CEH-14 and TTX-1 proteins with gcy-8 and gcy-18 promoters in vitro. The binding sites of CEH-14 and TTX-1 proteins were confirmed to be essential for AFD-specific expression of gcy-8 and gcy-18 in vivo. We also demonstrated that forced expression of CEH-14 and TTX-1 in AWB chemosensory neurons induced ectopic expression of gcy-8 and gcy-18 reporters in this neuron. Finally, we showed that the regulation of gcy-8 and gcy-18 expression by ceh-14 and ttx-1 is evolutionally conserved in five Caenorhabditis species. Taken together, ceh-14 and ttx-1 expression determines the fate of AFD as terminal selector genes at the final step of cell specification.
authors.affiliation: Genome Biology Laboratory, Center for Genetic Resource Information, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan; Transdisciplinary Research Integration Center, Research Organization of Information and Systems (ROIS), Toranomon 4-3-13, Minato-ku, Tokyo 105-0001, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kagoshima
authors.affiliation: Genome Biology Laboratory, Center for Genetic Resource Information, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan. Electronic address: ykohara@nig.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kohara
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D019295:Computational Biology; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D013045:Species Specificity; D013697:Thermosensing / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
chemical_list: C407044:CEH-14 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C438600:Ttx-1 protein, C elegans; D049452:Green Fluorescent Proteins; C511738:GCY-18 protein, C elegans; C511737:GCY-8 protein, C elegans; D006162:Guanylate Cyclase
keywords: Differentiation; Nematode; Neuron; Transcription factor