Transcriptional activation by ETS and leucine zipper-containing basic helix-loop-helix proteins

The immunoglobulin mu heavy-chain gene enhancer contains closely juxtaposed binding sites for ETS and leucine zipper-containing basic helix-loop-helix (bHLH-zip) proteins. To understand the mu enhancer function, we have inves tigated transcription activation by the combination of ETS and bHLH-zip pro teins. The bHLH-zip protein TFE3, but not USF, cooperated with the ETS doma in proteins PU.1 and Ets-1 to activate a tripartite domain of this enhancer . Deletion mutants sere used to identify the domains of the proteins involv ed. Both TFE3 and USF enhanced Ets-1 DNA binding in vitro by relieving the influence of an autoinhibitory domain in Ets-1 by direct protein-protein as sociations. Several regions of Ets-1 were found to be necessary, whereas th e bHLH-zip domain was sufficient for this effect. Our studies define novel interactions between ETS and bHLH-zip proteins that may regulate combinator ial transcription activation by these protein families.