COOPERATIVE DNA-BINDING OF THE BOVINE PAPILLOMAVIRUS-E2 TRANSCRIPTIONAL ACTIVATOR IS ANTAGONIZED BY TRUNCATED E2-POLYPEPTIDES

Cooperative DNA binding of the bovine papillomavirus type 1 (BPV-1) E2 transcriptional activator (E2-TA) is thought to play a role in the tr anscriptional synergism of multiple E2-responsive DNA elements (J. Ham , N. Dostatni, J.-M. Gauthier, and M. Yaniv, Trends Biochem. Sci. 16:4 40 444, 1991). Binding-equilibrium considerations show that such invol vement is unlikely, thereby suggesting that the E2-TA cooperative capa city may have evolved to play other, different roles. The role of coop erative interactions in the antagonistic activity of BPV-1-positive an d BPV-1-negative E2 regulatory proteins was investigated by an in vitr o quantitative gel shift assay. Viral repressor E2-TR, a truncated pep tide encompassing the activator DNA-binding domain, possesses a small but measurable cooperative capacity. Furthermore, the minimal E2 DNA-b inding domain interacts with the activator in a positive, heterocooper ative manner. As a result, the in vitro competition of full-length and truncated E2 peptides appears to be (macroscopically) noncooperative. This heterocooperative effect is probably dominant in latently infect ed G0-G1 cells, in which repressor E2-TR is 10- to 20-fold more abunda nt than the activator. The data are discussed considering the possible role of homo- and heterocooperative DNA binding in E2-conditional gen e expression.