Regulation of touch receptor differentiation by the Caenorhabditis elegans mec-3 and unc-86 genes.
The nematode Caenorhabditis elegans possesses six morphologically similar neurons that are responsible for sensing gentle touch to the body. Previous genetic studies identified genes that are necessary for the production and differentiation of these touch cells. In particular, unc-86 encodes a POU-type homeodomain protein needed for the production of the touch cells, while mec-3 encodes a LIM-type homeodomain protein needed for the differentiation of the touch cells. Molecular studies showed that MEC-3 and UNC-86 bind cooperatively to sites in the mec-3 promoter and can synergistically activate transcription from it in vitro. Here we show that UNC-86::MEC-3 hetero-oligomer-binding sites are also found in the promoters of two presumed targets of mec-3, the mec-4 and mec-7 genes, that are necessary for the function of the touch cells. These sites, which are well-conserved in the related nematode C. briggsae, are required for promoter activity. When one of the binding sites is cloned into a heterologous promoter, expression is found in the touch cells and two to four other cells that express mec-3 and unc-86. These data support a model in which touch-cell differentiation is specified, in part, by the UNC-86::MEC-3 hetero-oligomer and not by MEC-3 alone. Ectopic expression of mec-3, driven by a heat-shock promoter, also supports this hypothesis: the acquisition of touch-cell characteristics by several additional cells under these conditions required unc-86. Since the touch-cell lineages express UNC-86 before MEC-3, MEC-3 appears to modify the activity of UNC-86, leading to touch-cell-specific gene expression. Because both UNC-86 and MEC-3 have activation domains, the formation of the hetero-oligomer may create a strong activator. In the modification of UNC-86 function by MEC-3 in the touch cells, these studies provide an example of how the sequential activation of transcription factors can determine cell fate within particular cell lineages.
Duggan
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A
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Ma
C
C
Chalfie
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M
D000818:Animals; D002107:Caenorhabditis / Q000235:genetics; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002454:Cell Differentiation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018983:DNA Footprinting; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D017930:Genes, Reporter; D006360:Heat-Shock Proteins / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007473:Ion Channels / Q000235:genetics*; D060850:LIM-Homeodomain Proteins; D008465:Mechanoreceptors / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins; D016297:Mutagenesis, Site-Directed; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D050809:POU Domain Factors; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011984:Sensory Receptor Cells; D017384:Sequence Deletion; D013234:Stem Cells; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics*
D029742:Caenorhabditis elegans Proteins; D006360:Heat-Shock Proteins; D015801:Helminth Proteins; D018398:Homeodomain Proteins; D007473:Ion Channels; D060850:LIM-Homeodomain Proteins; C115871:Mec-4 protein, C elegans; C115872:Mec-7 protein, C elegans; D008565:Membrane Proteins; D050809:POU Domain Factors; D012333:RNA, Messenger; D014157:Transcription Factors; D014404:Tubulin; C072005:mec-3 protein, C elegans; C081539:unc-86 protein, C elegans