DNA binding and transcriptional activation by a PDX1 center dot PBX1b center dot MEIS2b trimer and cooperation with a pancreas-specific basic helix-loop-helix complex

In pancreatic acinar cells, the HOX-like factor PDX1 acts as part of a trim eric complex with two TALE class homeodomain factors, PBX1b and MEIS2b, The complex binds to overlapping half-sites for PDX1 and PBX, The trimeric com plex activates transcription in cells to a level about an order of magnitud e greater than PDX1 alone. The N-terminal PDX1 activation domain is require d for detectable transcriptional activity of the complex, even though PDX1 truncations bearing only the PDX1 C-terminal homeodomain and pentapeptide m otifs can still participate in forming the trimeric complex. The conserved N-terminal PBC-B domain of PBX, as well as its homeodomain, is required for both complex formation and transcriptional activity. Only the N-terminal r egion of MEIS2, including the conserved MEIS domains, is required for forma tion of a trimer on DNA and transcriptional activity: the MEIS homeodomain is dispensable. The activity of the pancreas-specific ELA1 enhancer require s the cooperation of the trimer-binding element and a nearby element that b inds the pancreatic transcription factor PTF1, We show that the PDX1 PBX1b. MEIS2b complex cooperates with the PTF1 basic helix-loop-helix complex to activate an ELA1 minienhancer in HeLa cells and that this cooperation requi res all three homeoprotein subunits, including the PDX1 activation domain.