C. elegans Rb, NuRD, and Ras regulate lin-39-mediated cell fusion during vulval fate specification.
The tumor suppressor Rb and the NuRD (nucleosome remodeling and histone deacetylation) complex have been implicated in transcriptional repression during cell cycle progression and cell fate specification. The Rb/E2F complex physically interacts with and thus recruits the NuRD complex to actively repress transcription. Caenorhabditis elegans counterparts of Rb, E2F/DP, and some NuRD complex components appear to function in a common class B synthetic Multivulva (synMuv) pathway to antagonize RTK/Ras signaling during vulval fate specification. Therefore, it has been suggested that they function together in a single complex to repress vulva-specific gene transcription. However, little is known about the in vivo interactions between these class B synMuv genes and their relationships with other pathways in specific cellular processes during vulval development. We show that C. elegans Rb/E2F and NuRD complexes antagonize Ras activity by controlling a lin-39 Hox-mediated cell fusion event that regulates the competence of vulval cells. Interestingly, Rb/E2F and NuRD complexes exhibit very different genetic properties. While the NuRD complex negatively regulates lin-39 Hox activity, likely by downregulating its expression, RB/E2F appears to play dual roles in regulating lin-39: a negative role in controlling its activity and a previously uncharacterized positive role in regulating its expression.
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Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, CO 80309, USA.
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D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002459:Cell Fusion; D019070:Cell Lineage; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005260:Female; D017238:Genes, Helminth; D006655:Histone Deacetylases / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D014157:Transcription Factors / Q000502:physiology*; D014844:Vulva / Q000166:cytology* / Q000254:growth & development; D018631:ras Proteins / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D018398:Homeodomain Proteins; D014157:Transcription Factors; C493765:efl-1 protein, C elegans; C108673:lin-39 protein, C elegans; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D018631:ras Proteins