General repression of enhanson activity by the adenovirus-2 E1A proteins.

It has been shown previously that the adenovirus 2 (Ad2) E1A proteins repress activation of transcription by the SV40, polyomavirus and immunoglobulin gene enhancers. Here, we demonstrate that the repression of the SV40 enhancer is not specifically mediated by one of its constituent enhansons and/or proto-enhancers, but that each is subject to repression individually. This inhibitory effect of the E1A proteins is also observed with the AP-1 factor-binding enhansons from the polyomavirus and human metallothionein enhancers, and the MHC class I gene H-2Kb enhanson, which binds the KBF1/H2TF1/TC-IIB protein. Repression by the E1A gene products may, in fact, extend to all enhancer trans-activators, because the transcriptional activities of nuclear receptors (e.g., the estrogen and glucocorticoid receptors), of the yeast enhancer factor GAL4 expressed in HeLa cells, and of chimeric trans-activators (such as GAL-VP16) are all similarly inhibited. The E1A protein domains 2 and 3, including the acidic amino acid stretch that has been shown previously to be necessary for E1A-mediated trans-activation, are not required for repression. These results indicate that the amino-terminal region of the protein, which contains domain 1, plays a crucial role in repression, possibly by interfering in the transcriptional activation process at a step common to all trans-acting enhancer factors.