Formation of α-Pal/Max heterodimers synergistically activates the eIF2- α promoter

Abstract

The transcription factor α-Pal recognizes two tandem palindromic repeats within the promoter of eukaryotic translation initiation factor 2-α (eIF2-α). Whereas both binding sites have the same 'core domain' sequence (CGCATGCG), they differ with respect to their flanking sequences. Of the two sites, the 5'-cap proximal site has a higher binding affinity for α-Pal than does the 5'-cap distal site (Jacob, W. F., Silverman, T. A., Cohen, R. B., and Safer, B. (1989) J. Biol. Chem. 264, 20372-20384). The well characterized transcription factor Max binds to sequences that are remarkably similar to the core domain that α-Pal recognizes. To date, all of the Max heterodimer partners lack DNA binding domains and are thus dependent on Max interacting with DNA. Here we report that the two α-Pal sites have very different binding activities with respect to the E-box-binding protein Max. The 5'-cap distal or low α-Pal affinity site binds both α-Pal and Max. Furthermore, both heterodimers and homodimers of each of these proteins bind to this site. In contrast to the low affinity site, the high affinity site does not bind Max as a homodimer. This is the first documented case where Max heterodimerizes with a transcription factor that has affinity for DNA independent of Max.