A domain necessary for the transforming activity of SnoN is required for specific DNA binding, transcriptional repression and interaction with TAFII110

Abstract

Sno is a member of the ski oncogene family and shares ski's ability to transform avian fibroblasts and induce muscle differentiation. Ski and Sno are nuclear proteins that form homodimers and heterodimers. Ski activates transcription of cellular and viral enhancers and we have identified a DNA binding site (GTCTAGAC) through which it represses transcription. In this work, we show that SnoN binds this site and represses transcription of reporters with this binding site as an upstream element. Using fusions with the Gal4-DNA binding domain in a heterologous reporter assay, we identify a tripartite repression domain in SnoN. A 107 amino acid stretch of the SnoN repression domain, that contains two of the subdomains, is closely related to the minimal region of Ski required for transformation. The third subdomain is unique to SnoN. By analysing deletions involving each of the subdomains, we show that subdomains II and III are also required for DNA binding and cellular transformation. We provide evidence for a quenching mechanism of transcriptional repression by which subdomain II binds to TAF(II)110.