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The RING finger/B-box factor TAM-1 and a retinoblastoma-like protein LIN-35 modulate context-dependent gene silencing in Caenorhabditis elegans.

Genes & development | Nov 15, 1999

http://www.ncbi.nlm.nih.gov/pubmed/10580003

Context-dependent gene silencing is used by many organisms to stably modulate gene activity for large chromosomal regions. We have used tandem array transgenes as a model substrate in a screen for Caenorhabditis elegans mutants that affect context-dependent gene silencing in somatic tissues. This screen yielded multiple alleles of a previously uncharacterized gene, designated tam-1 (for tandem-array-modifier). Loss-of-function mutations in tam-1 led to a dramatic reduction in the activity of numerous highly repeated transgenes. These effects were apparently context dependent, as nonrepetitive transgenes retained activity in a tam-1 mutant background. In addition to the dramatic alterations in transgene activity, tam-1 mutants showed modest alterations in expression of a subset of endogenous cellular genes. These effects include genetic interactions that place tam-1 into a group called the class B synMuv genes (for a Synthetic Multivulva phenotype); this family plays a negative role in the regulation of RAS pathway activity in C. elegans. Loss-of-function mutants in other members of the class-B synMuv family, including lin-35, which encodes a protein similar to the tumor suppressor Rb, exhibit a hypersilencing in somatic transgenes similar to that of tam-1 mutants. Molecular analysis reveals that tam-1 encodes a broadly expressed nuclear protein with RING finger and B-box motifs.

Pubmed ID: 10580003 RIS Download

Mesh terms: Amino Acid Sequence | Animals | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Gene Silencing | Genes, ras | Helminth Proteins | Molecular Sequence Data | Muscle Proteins | Nuclear Proteins | Phenotype | Repressor Proteins | Sequence Alignment | Signal Transduction | Transgenes

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Associated grants

  • Agency: NIGMS NIH HHS, Id: GM37706
  • Agency: NICHD NIH HHS, Id: HD23690
  • Agency: NIGMS NIH HHS, Id: R01 GM037706
  • Agency: NIGMS NIH HHS, Id: T32GM07231

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