EcR interacts with corepressors and harbours an autonomous silencing domain functional in both Drosophila and vertebrate cells.

The ecdysone receptor (EcR) is a member of the large family of nuclear horm one receptors, which are ligand regulated transcription factors. rn general , ligand converts these receptors into a transcriptional activator. Some ve rtebrate nuclear hormone receptors, such as the thyroid hormone and retinoi c acid receptors, silence gene expression in the absence of ligand. EcR is involved in fly metarmorphosis and is used in vertebrates as an inducible s ystem for expression of transgenes. Here, we show that a Drosophila recepto r, the EcR, harbours an autonomous silencing function in its carboxy-termin us. Interestingly, EcR mediates also silencing in vertebrate cells. In conc ordance with this EcR interacts with the corepressors SMRT and N-CoR, while addition of ligand reduces this interaction. Conversely, the v-erbA oncoge ne product, a thyroid hormone receptor derivative, mediates silencing in Dr osophila cells. Thus, our data suggest the involvement of an evolutionarily conserved mechanism by which nuclear hormone receptors mediate gene silenc ing in multicellular organisms. (C) 1999 Elsevier Science Ltd. All rights r eserved.