Sμbp-2 Represses the Epstein–Barr Virus Lytic Switch Promoter

Abstract

Sμbp-2 is a novel transcription factor that was first identified through its interaction with the immunoglobulin Sμ region (Mizuta et al., 1993) and has been cloned by virtue of its binding to two 12-O-tetradecanoylphorbol-13-acetate-responsive elements in the Epstein–Barr virus immediate-early BZLF1 promoter (Gulley et al., 1997). In this report, we examined the effect of Sμbp-2 overexpression on BZLF1 promoter activity. Overexpression of Sμbp-2 in the B lymphocyte cell line BJAB caused repression of the BZLF1 gene promoter. A 14-bp region that partially overlaps with a 12-O-tetradecanoylphorbol-13-acetate-responsive element was required for maximal repression by Sμbp-2, but some repression was also seen with a minimal promoter containing only the BZLF1 promoter TATA box and an initiation site. A 30-bp fragment containing the 14-bp region could transfer Sμbp-2-mediated repression to heterologous promoters. Sμbp-2 was found to associate with the basal transcription factor TATA binding protein (TBP) and to disrupt the formation of a stable TBP–TFIIA–DNA complex on the BZLF1 promoter TATA box and the adenovirus E1B promoter TATA box. Repression of the BZLF1 promoter by overexpressed Sμbp-2 was rescued by overexpression of the basal factor TFIIA. These results suggest that complete repression of the BZLF1 promoter by Sμbp-2 involves disruption of a functional TBP–TFIIA–TATA box complex and requires the −93 bp-to-−79 bp region of the promoter.