Cosuppression of nonhomologous transgenes in Drosophila involves mutually related endogenous sequences

Cosuppression refers to the phenomenon in which silencing among dispersed h omologous genes occurs. Here we demonstrate that two nonhomologous reciproc al fusion genes, white-Alcohol dehydrogenase (w-Adh) and Adh-w, exhibit cos uppression using the endogenous Adh sequence as an intermediary. Deletion o f the endogenous Adh gene eliminates the interaction, while reintroduction of an 8.6 kb Adh fragment restores the silencing. Using truncated Adh const ructs, a nontranscribed segment in the Adh regulatory region was found to b e one of the sequences required for homology recognition. The silencing int eraction is initiated during early development. The silenced transgenes are associated with the Polycomb group complex of chromatin proteins.