Two functionally distinct domains responsible for transactivation by the Ets family member ERM

The recently cloned human Ets transcription factor ERM is closely related to the ER81 and PEA3 genes. Here, we report the functional analysis of the DNA-binding and transactivation properties of ERM. Specific DNA-binding by ERM requires the ETS domain, conserved in all members of the Ets family and is inhibited by an 84 residue long central region and the carboxy-terminal tail. Two fragments of ERM are transferrable activation domains: α which sits in the 72 first residues and encompasses the acidic domain conserved between ERM, ER81 and PEA3, and the carboxy-terminal tail which also bears a DNA-binding inhibition function. Deletion of α strongly reduces transactivation by ERM. Moreover, α and the carboxyterminal tail exhibit functional synergism, suggesting that they activate transcription through different mechanisms. In support of this idea, we demonstrate that VP16 squelches transactivation by α but not by the carboxyterminal tail. This result also indicates that α and VP16 may share common limiting cofactors. α and the carboxy-terminal tail do not seem to be conserved within the whole Ets family, indicating that the specificity of ERM may rely on interactions with distinct cofactors.