Cloning and characterization of the EAP30 subunit of the ELL complex that confers derepression of transcription by RNA polymerase II

The product of the human oncogene ELL encodes an RNA polymerase II transcri ption factor that undergoes frequent translocation in acute myeloid leukemi a (AML), In addition to its elongation activity, ELL contains a novel type of RNA polymerase II interaction domain that is capable of repressing polym erase activity in promoter-specific transcription. Remarkably, the ELL tran slocation that is found in patients with AML results in the deletion of exa ctly this functional domain. Here we report that the EAP30 subunit of the E LL complex has sequence homology to the Saccharomyces cerevisiae SNF8, whos e genetic analysis suggests its involvement in the derepression of gene exp ression. Remarkably, EAP30 can interact with ELL and derepress ELL's inhibi tory activity in vitro. This finding may reveal a key role for EAP30 in the pathogenesis of human leukemia.