Characterization of a nuclear factor, papilloma enhancer binding factor‐1, that binds the long control region of human papillomavirus type 16 and contributes to enhancer activity

Abstract

Human papillomavirus type‐16 (HPV‐16) is an epitheliotropic DNA tumor virus associated with the development of cervical carcinoma. The expression of HPV‐16 early genes is driven by a cell‐type—specific enhancer located in the long control region of the viral genome. We identified an element within the HPV‐16 minimal enhancer that has enhancer activity and binds a nuclear factor, designated papillomavirus enhancer binding factor‐1 (PEF‐1). The element (called FP‐F by us and fp5e by Gloss et al. (EMBO J 6:3735–3743, 1987)) was originally identified as a footprint by DNase I protection experiments. The PEF‐1 binding site is centered around a CCAAT box—like CCAAC element. Introduction of A→T transversions into the CCAAC element of fp5e abolished binding of PEF‐1 and concomitantly abolished enhancer function. fp5e resembles binding sites for the transcriptional activators CTF/NF‐1 and AP‐2; however, we showed that neither of these factors interacted with this element. PEF‐1 has an apparent molecular weight of about 110 kDa, and we propose that it is a novel factor involved in the transcriptional activation of HPV‐16 gene expression.