Mechanism of action of the papillomavirus E2 repressor: repression in the absence of DNA binding.

Repression of papillomavirus E2-dependent gene expression was studied by using transient transfections into mouse embryo fibroblast cells. Cotransfection of a gene corresponding to the naturally occurring repressor E2-TR along with the full-length E2 gene resulted in up to 98% repression of E2-dependent reporter gene expression. A series of E2 DNA-binding domain mutants were transferred into the E2-TR form and characterized for their ability to repress E2-dependent transactivation. All mutants which were defective for DNA binding but were dimerization competent repressed E2 transactivation as well or nearly as well as the wild-type repressor. E2 mutants which lacked dimerization activity repressed transactivation poorly or not at all. These results indicate that the E2 repressor can inhibit transcription, in the absence of DNA binding, by forming heterodimers with full-length E2.