Epstein-Barr Virus Small RNA (EBER) Genes: Unique Transcription Units That Combine RNA Polymerase II and III Promoter Elements

The Epstein-Barr virus-encoded small RNA (EBER) genes appear to comprise an interesting subset of class III genes different from any previously identified, including U6 and 7SK. EBER genes have functional A and B box intragenic control regions. In addition, they contain three upstream elements that together stimulate in vivo expression 50-fold and resemble sites associated with typical class II promoters. DNAase I footprinting analyses using purified proteins or oligonucleotide competition demonstrate that nucleotides -40 to -55 bind activating transcription factor (ATF) or a related protein, while nucleotides -56 to -77 bind Sp1 protein or a related protein. The element between positions -23 and -28 resembles a TATA box. EBERs are unusual RNA polymerase III transcripts shown to be controlled by ATF- and Sp1-like promoter elements, suggesting mechanisms for their high level expression in EBV-transformed lymphocytes.