The mammalian basic helix loop helix protein HES-1 binds to and modulates the transactivating function of the Runt-related factor Cbfa1

Drosophila Runt is the founding member of a family of related transcription factors involved in the regulation of a variety of cell-differentiation ev ents in invertebrates and vertebrates. Runt-related proteins act as both tr ansactivators and transcriptional repressors, suggesting that context-depen dent mechanisms modulate their transcriptional properties. The aim of this study was to elucidate the molecular mechanisms that contribute to the regu lation of the functions of the mammalian Runt-related protein, Cbfa1. Here we provide the first demonstration that Cbfa1 (as well as the related prote in, Cbfa2/AML1) physically interacts with the basic helix loop helix transc ription factor, HES-1, a mammalian counterpart of the Drosophila Hairy and Enhancer of split proteins. This interaction is mediated by the carboxyl-te rminal domains of Cbfa1 and HES-1, but does not require their respective te trapeptide motifs, WRPY and WRPW. Our studies also show that HES-1 can anta gonize the binding of Cbfa1 to mammalian transcriptional corepressors of th e Groucho family. Moreover, HES-1 can potentiate Cbfa1-mediated transactiva tion in transfected cells. Taken together, these findings implicate HES-1 i n the transcriptional functions of Cbfa1 and suggest that the concerted act ivities of Groucho and HES proteins modulate the functions of mammalian Hun t-related proteins.