FUNCTIONAL INTERACTION BETWEEN THE POU DOMAIN PROTEIN TST-1 OCT-6 ANDTHE HIGH-MOBILITY-GROUP PROTEIN HMG-I/Y/

The POU domain protein Tst-1/Oct-6 is a transcriptional activator of h uman papovavirus JC virus in transient transfections. Because of its e ndogenous expression in myelinating glia, Tst-1/Oct-6 might also be an important determinant for the glia specificity of JC virus in vivo. A ctivation of viral early and late genes depends on the ability of Tst- 1/Oct-6 to interact with an AT-rich element within the viral regulator y region. Here, we show that this element not only is bound by Tst-1/O ct-6 but, in addition, serves as a binding site for the high-mobility- group protein HMG-I/Y. In the presence of HMG-I/Y, Tst-1/Oct-6 exhibit ed an increased affinity for this AT-rich element. The specificity of this effect was evident from the fact that no stimulation of Tst-1/Oct -6 binding was observed on a site that did not allow binding of HMG-I/ Y. In addition, both proteins interacted with each other in solution. Direct contacts were identified between the POU domain of Tst-1/Oct-6 and a short stretch of 10 amino acids in the central portion of HMG-I/ Y. These results point to an accessory role for HMG-I/Y in the activat ion of JC viral gene expression by the POU domain protein Tst-1/Oct-6 In agreement with such a role, HMG-Y synergistically supported the fun ction of Tst-1/Oct-6 in transient transfections, measured on the early promoter of JC virus or on an artificial promoter consisting of only a TATA box and the common binding element for Tst-1 and HMG-I/Y.