GROUCHO-DEPENDENT AND GROUCHO-INDEPENDENT REPRESSION ACTIVITIES OF RUNT DOMAIN PROTEINS

Runt domain proteins are transcriptional regulators that specify cell fates for processes extending from pattern formation in insects to leu kemogenesis in humans. Runt domain family members are defined based on the presence of the 128-amino-acid Runt domain, which is necessary an d sufficient for sequence-specific DNA binding. We demonstrate an evol utionarily conserved protein-protein interaction between Runt domain p roteins and the corepressor Groucho. The interaction, however, is inde pendent of the Runt domain and can be mapped to a 5-amino-acid sequenc e, VWRPY, present at the C terminus of all Runt domain proteins. Droso phila melanogaster Runt and Groucho interact genetically; the in vivo repression of a subset of Runt-regulated genes is dependent on the int eraction with Groucho and is sensitive to Groucho dosage. Runt's repre ssion of one gene, engrailed, is independent of VWRPY and Groucho, thu s demonstrating alternative mechanisms for repression by Runt domain p roteins. Unlike other transcriptional regulatory proteins that interac t with Groucho, Runt domain proteins are known to activate transcripti on. This suggests that the Runt domain protein-Groucho interaction may he regulated.