RRC ID 3405
Author Andersen EC, Lu X, Horvitz HR.
Title C. elegans ISWI and NURF301 antagonize an Rb-like pathway in the determination of multiple cell fates.
Journal Development
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.
Volume 133(14)
Pages 2695-704
Published 2006-7
DOI 10.1242/dev.02444
PII dev.02444
PMID 16774993
MeSH 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
IF 5.413
Times Cited 40
WOS Category DEVELOPMENTAL BIOLOGY
Resource
C.elegans tm1489 tm235