Different transcriptional properties of mSim-1 and mSim-2

The mSim-1 and mSim-2 gene products are mammalian homologues of the Drosophila Sim gene. The dSim gene product transactivates through a DNA binding site known as the CNS midline enhancer (CME) element. We have investigated the transcriptional properties of mSIM-1 and mSIM-2 mediated through the CME element in concert with their dimerization partners, ARNT and ARNT-2. The mSIM-1/ARNT heterodimer transactivates reporter constructs via the ARNT carboxy-terminus. However, mSIM-2 quenches ARNT transactivation. We find that mSIM-2 competes with mSIM-1 for binding to ARNT, suggesting a possible antagonism between these transcription factors.