A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia

AML1 is one of the most frequently translocated genes in human leukemia. He re we demonstrate that acute myeloid leukemia-1 (AML-1) (Runx-1) represses transcription from a native promoter, p21(Waf1/Cip1). Unexpectedly, this re pression did not require interactions with the Groucho co-repressor. To def ine the mechanism of repression, we asked whether other co-repressors could interact with AML-1. We demonstrate that AML-1 interacts with the mSin3 co -repressors. Moreover, endogenous AML-1 associated with endogenous mSin3A i n mammalian cells. A deletion mutant of AML-1 that did not interact with mS in3A failed to repress transcription. The AML-1/mSin3 association suggests a mechanism of repression for the chromosomal translocation fusion proteins that disrupt AML-1.