Epstein-Barr Virus oncoprotein super-enhancers control B cell growth
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ABSTRACT: Super-enhancers are principal determinants of cell transcription, development, phenotype, and oncogenesis, not yet implicated in host-pathogen interactions. We found four Epstein-Barr virus (EBV) oncoproteins and five EBV-activated NF-B subunits co-occupying thousand of enhancer sites in EBV-transformed lymphoblastoid cells (LCLs). Of these, 187 had markedly higher and broader histone H3K27ac signals characteristic of super-enhancer formation, and were designated “EBV super-enhancers”. EBV super-enhancer associated genes included MYC and BCL2, which enable LCL proliferation and survival. EBV super-enhancers were enriched for specific B cell transcription factor motifs and had high STAT5 and NFAT co-occupancy. EBV super-enhancer associated genes were more highly expressed than other LCL genes. Disruption of EBV super-enhancers by the bromo-domain inhibitor, JQ1, by conditional inactivation of an EBV oncoprotein or NF-B, decreased MYC or BCL2 gene expression and arrested LCL growth. These findings provide novel insights into the mechanisms by which EBV causes lymphoproliferation and identify opportunities for therapeutic intervention.
ORGANISM(S): Homo sapiens
PROVIDER: GSE62912 | GEO | 2014/11/01
SECONDARY ACCESSION(S): PRJNA266020
REPOSITORIES: GEO
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