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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.

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


  • Hsieh J
  • Liu J
  • Kostas SA
  • Chang C
  • Sternberg PW
  • Fire A


Genes & development

Publication Data

November 15, 1999

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

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