A CONDITIONAL VERSION OF THE ETS TRANSCRIPTION FACTOR ERM BY FUSION TO THE LIGAND-BINDING DOMAIN OF THE ESTROGEN-RECEPTOR

The fusion of a wide range of proteins to the ligand-binding domain of nuclear receptors has been shown to impart ligand-dependent inducible activity of the resulting chimera. Transcriptional regulators of the ETS family are involved in both normal and oncogenic processes. In ord er to address the role of Erm, a ''PEA3 subgroup'' member of this fami ly, we generated a chimera between Erm and the widely used ligand-bind ing domain of the oestrogen receptor (ER). The chimera, ErmER, consist s of Erm protein fused at its C-terminal end to the ER domain. We show that ErmER displays a ligand-dependent transcriptional activity on et s responsive elements. The efficiency of ErmER mediated transactivatio n is modulated by the hormone concentration while its weak leakiness i s reduced by using the steroidal anti-oestrogen EM-139. Our results de fine ErmER as the first conditional version of an Ets transcription fa ctor, providing a useful tool to decipher Erm biological role and to i dentify potential Erm target genes. (C) 1997 Academic Press.