Identification of the region of mi transcription factor which is responsible for the synergy with PEBP2/CBF

The mi locus encodes the mi transcription factor (MITF), a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors. MITF binds the αB1/AML1 subtype of the α subunit of the polyomavirus enhancer binding protein 2 (PEBP2). These two transcription factors synergistically transactivate the mouse mast cell protease 6 (MMCP-6) gene. The interaction of PEBP2 with MITF is mediated through the region carboxy-terminal to the DNA-binding Runt domain. In the present study, we examined the region of MITF that is responsible for the interaction with PEBP2. The MITF mutant that lacked the region aa 67-152 did not bind PEBP2, and the mutant that lacked the region aa 1-152 lost the synergistic function in the transactivation of the MMCP-6 promoter. We conclude that the region amino-terminal to the basic region of MITF is required for physical and functional interactions with PEBP2.