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PMID:16774993

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Citation

Andersen, EC, Lu, X and Horvitz, HR (2006) C. elegans ISWI and NURF301 antagonize an Rb-like pathway in the determination of multiple cell fates. Development 133:2695-704

Abstract

The class A, B and C synthetic multivulva (synMuv) genes act redundantly to negatively regulate the expression of vulval cell fates in Caenorhabditis elegans. The class B and C synMuv proteins include homologs of proteins that modulate chromatin and influence transcription in other organisms similar to members of the Myb-MuvB/dREAM, NuRD and Tip60/NuA4 complexes. To determine how these chromatin-remodeling activities negatively regulate the vulval cell-fate decision, we isolated a suppressor of the synMuv phenotype and found that the suppressor gene encodes the C. elegans homolog of Drosophila melanogaster ISWI. The C. elegans ISW-1 protein likely acts as part of a Nucleosome Remodeling Factor (NURF) complex with NURF-1, a nematode ortholog of NURF301, to promote the synMuv phenotype. isw-1 and nurf-1 mutations suppress both the synMuv phenotype and the multivulva phenotype caused by overactivation of the Ras pathway. Our data suggest that a NURF-like complex promotes the expression of vulval cell fates by antagonizing the transcriptional and chromatin-remodeling activities of complexes similar to Myb-MuvB/dREAM, NuRD and Tip60/NuA4. Because the phenotypes caused by a null mutation in the tumor-suppressor and class B synMuv gene lin-35 Rb and a gain-of-function mutation in let-60 Ras are suppressed by reduction of isw-1 function, NURF complex proteins might be effective targets for cancer therapy.

Links

PubMed Online version:10.1242/dev.02444

Keywords

Adenosine Triphosphatases/genetics; Adenosine Triphosphatases/metabolism; Animals; Caenorhabditis elegans/anatomy & histology; Caenorhabditis elegans/embryology; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cell Lineage; Chromatin/metabolism; Chromosomal Proteins, Non-Histone/genetics; Chromosomal Proteins, Non-Histone/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Humans; Morphogenesis; Multiprotein Complexes; Phenotype; RNA Interference; Retinoblastoma Protein/genetics; Retinoblastoma Protein/metabolism; Signal Transduction/physiology; Transcription Factors/genetics; Transcription Factors/metabolism; ras Proteins/genetics; ras Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:ISW1

located_in

GO:0000785: chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:ISW1

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003036
WB:WBGene00023498

P

Seeded From UniProt

complete


See also

References

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