title: BIM promoter directly targeted by EBNA3C in polycomb-mediated repression by EBV.
abstract: Detailed analyses of the chromatin around the BIM promoter has revealed that latent Epstein-Barr virus (EBV) triggers the recruitment of polycomb repressive complex 2 (PRC2) core subunits and the trimethylation of histone H3 lysine 27 (H3K27me3) at this locus. The recruitment is absolutely dependent on nuclear proteins EBNA3A and EBNA3C; what is more, epitope-tagged EBNA3C could be shown bound near the transcription start site (TSS). EBV induces no consistent changes in the steady-state expression of PRC2 components, but lentivirus delivery of shRNAs against PRC2 and PRC1 subunits disrupted EBV repression of BIM. The activation mark H3K4me3 is largely unaltered at this locus irrespective of H3K27me3 status, suggesting the establishment of a 'bivalent' chromatin domain. Consistent with the 'poised' nature of these domains, RNA polymerase II (Pol II) occupancy was not altered by EBV at the BIM TSS, but analysis of phospho-serine 5 on Pol II indicated that EBNA3A and EBNA3C together inhibit initiation of BIM transcripts. B cell lines carrying EBV encoding a conditional EBNA3C-oestrogen receptor-fusion revealed that this epigenetic repression of BIM was reversible, but took more than 3 weeks from when EBNA3C was inactivated.
authors.affiliation: Section of Virology, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, UK.
authors.forename: Kostas
authors.initials: K
authors.lastname: Paschos
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Parker
authors.forename: Ekularn
authors.initials: E
authors.lastname: Watanatanasup
authors.forename: Robert E
authors.initials: RE
authors.lastname: White
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Allday
mesh_terms: D000956:Antigens, Viral / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D000072224:Bcl-2-Like Protein 11; D002460:Cell Line; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012319:RNA Polymerase II / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000956:Antigens, Viral; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C508151:EBNA-3A antigen; C498774:EBNA-3C, epstein-barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D006657:Histones; D008565:Membrane Proteins; D063146:Polycomb-Group Proteins; D021122:Protein Subunits; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; D012319:RNA Polymerase II