Functional silencing of chromosomal loci can be induced by transgenes (cosu
ppression) or by introduction of double-stranded RNA (RNAi). Here, we demon
strate the generality of and define rules for a transgene-mediated cosuppre
ssion phenomenon in the Caenorhabditis elegans germ line. Functional repres
sion is not a consequence of persistent physical association between transg
enes and endogenous genes or of mutations in affected genes. The cosuppress
ion mechanism likely involves an RNA mediator that defines its target speci
ficity, reminiscent of RNAi. Cosuppression is strongly abrogated in rde-2 a
nd mut-7 mutants, but is not blocked in an rde-1 mutant, indicating that co
suppression and RNAi have overlapping but distinct genetic requirements.