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.
Hsieh
J
J
Carnegie Institution of Washington, Department of Embryology, Baltimore, Maryland 21210, USA.
Liu
J
J
Kostas
S A
SA
Chang
C
C
Sternberg
P W
PW
Fire
A
A
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D020868:Gene Silencing; D011905:Genes, ras; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D015398:Signal Transduction; D019076:Transgenes
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D015801:Helminth Proteins; C116486:LIN-53 protein, C elegans; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C402463:TAM-1 protein, C elegans; C116485:lin-35 protein, C elegans