2 FUNCTIONALLY DISTINCT DOMAINS RESPONSIBLE FOR TRANSACTIVATION BY THE ETS FAMILY MEMBER ERM

The recently cloned human Ets transcription factor ERM is closely rela ted to the ER81 and PEA3 genes. Here, we report the functional analysi s of the DNA-binding and transactivation properties of ERM. Specific D NA-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: alpha, which sits in the 72 first residues and enc ompasses the acidic domain conserved between ERM, ER81 and PEA3, and t he carboxy-terminal tail which also bears a DNA-binding inhibition fun ction. Deletion of alpha strongly reduces transactivation by ERM. More over, alpha and the carboxyterminal tail exhibit functional synergism, suggesting that they activate transcription through different mechani sms. In support of this idea, we demonstrate that VP16 squelches trans activation by alpha but not by the carboxyterminal tail. This result a lso indicates that alpha and VP16 may share common limiting cofactors. alpha and the carboxy-terminal tail do not seem to be conserved withi n the whole Ets family, indicating that the specificity of ERM may rel y on interactions with distinct cofactors.