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

Jenny Hsieh, Jing Liu, Stephen A. Kostas, Chieh Chang, Paul W. Sternberg, Andrew Fire

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2958-2970
Number of pages13
JournalGenes and Development
Volume13
Issue number22
DOIs
StatePublished - 1999

Keywords

  • C. elegans
  • Chromatin Silencing
  • RAS Pathway
  • RING finger
  • Rb
  • TAM-1

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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