MECHANISMS FOR FLEXIBILITY IN DNA-SEQUENCE RECOGNITION AND VP16-INDUCED COMPLEX-FORMATION BY THE OCT-1 POU DOMAIN

DNA binding by the Oct-1 protein is directed by its POU domain, a bipa rtite DNA-binding domain made up of a POU-specific (POUS) domain and a POU-homeo (POUH) domain, two helix-turn-helix-containing DNA-binding modules that cooperate in DNA recognition. Although the best-character ized DNA target for Oct-1 binding is the octamer sequence ATGCAAAT, Oc t-1 also binds a number of different DNA sequence elements. For exampl e, Oct-1 recognizes a form of the herpes simplex virus VP16-responsive TAATGARAT element, called the (OCTA(-))TAATGARAT site, that lacks oct amer site similarity. Our studies suggest two mechanisms by which Oct- 1 achieves flexible DNA sequence recognition. First, an important argi nine found in the Oct-1 POUS domain tolerates substitutions of its bas e contacts within the octamer site. Second, on the (OCTA(-))TAATGARAT site, the POUS domain is located on the side of the POUH domain opposi te from where it is located on an octamer site. This flexibility of th e Oct-1 POU domain in DNA binding also has an impact on its participat ion in a multiprotein-DNA complex with VP16. We show that Oct-1 POUS d omain residues that contact DNA have different effects on VP16-induced complex formation depending on whether the VP16-responsive element in volved has overlapping octamer similarity or not.