ABSTRACT: Epstein-Barr-Virus (EBV) Nuclear Antigens EBNALP and EBNA2 are co-expressed in EBV infected B-lymphocytes and are critical for Lymphoblastoid Cell Line (LCL) growth. EBNALP removes NCOR1 and RBPJ repressive complexes from promoter and enhancer sites and EBNA2 mostly activates transcription from distal enhancers. ChIP-seqs found EBNALP at 19,224 LCL sites, which were 33% promoter associated. EBNALP was associated with 10 transcription factor (TF) clusters that included YY1(63%), SP1(62%), PAX5(59%), BATF(50%), IRF4(49%), RBPJ(43%), ETS1(39%), PU.1(37%), RAD21(33%), NF-kB(31%), TBLR1(26%), ZNF143(24%), CTCF(23%), SMC3(21%), and EBF(17%). EBNALP sites had higher H3K4me3, H3K9ac, H3K27ac, H2Az, and RNA Pol II signals than EBNA2 sites and had similar transcription effects. EBNALP co-localized with 29% of 19,845 EBNA2 sites. EBNALP/EBNA2 sites were similar to EBNALP sites in promoter localization, associated cell TFs, Pol II, H3K4me3, H3K9ac, H3K27ac, and H2Az signals. EBNALP and EBNA2 promoter sites were more transcriptionally active than EBNALP or EBNA2 promoter sites. EBNALP was at the enhancer or promoter of myc and MYC affected genes, including cyclin D2, and bcl2. EBNALP at promoters with DNA looping and transcription factors, is positioned to deplete repressors from enhancers and promoters, enable chromatin remodeling, and transcription activation.
