TLE, the human homolog of Groucho, interacts with AML1 and acts as a repressor of AML1-induced transactivation

The AML1 gene encodes DNA-binding proteins that contain the Runt domain and is found at the breakpoints of some translocations associated with leukemi as. It has been reported that AML1 plays pivotal roles in myeloid different iation, probably through the transcriptional regulation of various hematopo ietic genes. Here we demonstrate the physical and the functional interactio n between AML1 and TLE1 (transducin-like Enhancer of split) human homolog o f Groucho that is known to be a corepressor of Hairy-related proteins. TLE1 binds to AML1 through the Runt domain and the C terminus of AML1 that incl udes the VWRPY motif. The interaction is mainly mediated by the SP domain o f TLE1. Moreover, TLE1 inhibits AML1-induced transactivation of the target promoters through the C terminus of AML1. These results suggest that TLE1 a cts as a repressor of AML1 and provide important insights into the mechanis m of the negative regulation of the AML1 functions in hematopoiesis and leu kemogenesis. (C) 1998 Academic Press.