@article {352476,
	title = {Epstein-Barr virus nuclear antigen 3A partially coincides with EBNA3C genome-wide and is tethered to DNA through BATF complexes},
	journal = {Proc Natl Acad Sci U S A},
	volume = {112},
	number = {2},
	year = {2015},
	month = {2015 Jan 13},
	pages = {554-9},
	abstract = {Epstein-Barr Virus (EBV) conversion of B-lymphocytes to Lymphoblastoid Cell Lines (LCLs) requires four EBV nuclear antigen (EBNA) oncoproteins: EBNA2, EBNALP, EBNA3A, and EBNA3C. EBNA2 and EBNALP associate with EBV and cell enhancers, up-regulate the EBNA promoter, MYC, and EBV Latent infection Membrane Proteins (LMPs), which up-regulate BCL2 to protect EBV-infected B-cells from MYC proliferation-induced cell death. LCL proliferation induces p16(INK4A) and p14(ARF)-mediated cell senescence. EBNA3A and EBNA3C jointly suppress p16(INK4A) and p14(ARF), enabling continuous cell proliferation. Analyses of the EBNA3A human genome-wide ChIP-seq landscape revealed 37\% of 10,000 EBNA3A sites to be at strong enhancers; 28\% to be at weak enhancers; 4.4\% to be at active promoters; and 6.9\% to be at weak and poised promoters. EBNA3A colocalized with BATF-IRF4, ETS-IRF4, RUNX3, and other B-cell Transcription Factors (TFs). EBNA3A sites clustered into seven unique groups, with differing B-cell TFs and epigenetic marks. EBNA3A coincidence with BATF-IRF4 or RUNX3 was associated with stronger EBNA3A ChIP-Seq signals. EBNA3A was at MYC, CDKN2A/B, CCND2, CXCL9/10, and BCL2, together with RUNX3, BATF, IRF4, and SPI1. ChIP-re-ChIP revealed complexes of EBNA3A on DNA with BATF. These data strongly support a model in which EBNA3A is tethered to DNA through a BATF-containing protein complexes to enable continuous cell proliferation.},
	keywords = {B-Lymphocytes, Basic-Leucine Zipper Transcription Factors, Binding Sites, Cell Line, Chemokine CXCL10, Chemokine CXCL9, Core Binding Factor Alpha 3 Subunit, Cyclin D2, dna, Enhancer Elements, Genetic, Epstein-Barr Virus Nuclear Antigens, Genes, bcl-2, Genes, myc, Genes, p16, Genome, Human, Genome, Viral, Herpesvirus 4, Human, Host-Pathogen Interactions, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Interferon Regulatory Factors, Promoter Regions, Genetic, Viral Proteins},
	issn = {1091-6490},
	doi = {10.1073/pnas.1422580112},
	author = {Schmidt, Stefanie C S and Jiang, Sizun and Zhou, Hufeng and Willox, Bradford and Holthaus, Amy M and Kharchenko, Peter V and Johannsen, Eric C and Kieff, Elliott and Zhao, Bo}
}
