A cellular transcription factor E4F1 interacts with an E1a-inducible enhancer and mediates constitutive enhancer function in vitro.

Efficient transcription of the adenovirus E1a-inducible E4 gene is mediated by an E1a-dependent enhancer in vivo. In vitro, the enhancer functions constitutively in the absence of E1a, conferring high levels of transcription on the E4 and heterologous promoters. Binding of a cellular transcription factor, E4F1, to two sites within the E4 enhancer and to one other functionally important site located directly upstream of the E4 TATA box is required for transcriptional activity. The relationship between the enhancer and the TATA box proximal site is further demonstrated by the fact that the E4 enhancer can be functionally substituted by two copies of the TATA box proximal site. These and other results suggest that the E4 promoter may be comprised solely of multiple E4F1 binding sites and a TATA box. In addition to the E4 promoter, E4F1 interacts with other adenovirus early promoters and thus may be involved in the co-ordinate expression of E1a-inducible early viral genes.