title: The role of DNA hypomethylation, histone acetylation and in vivo protein-DNA binding in Epstein-Barr virus-induced CD23 upregulation.
abstract: We analyzed epigenetic marks at the CD23 regulatory regions in well characterized Epstein-Barr virus (EBV)-carrying cell lines covering the major latency types. Bisulfite sequencing showed that DNA methylation is not a major regulator of EBV-induced CD23 transcription, although a wide hypomethylated DNA sequence in the regulatory regions is always present in the cell lines with high CD23 expression. Acetylated histone H3 levels at the CD23b promoter showed strong correlation with CD23b expression, while a weaker correlation could be observed at the CD23a core promoter. DMS in vivo footprinting at the intronic EBV-responsive enhancer and the intermediate-affinity CBF1 site at the CD23a core promoter did not reveal any significant sign of in vivo protein-DNA interactions, despite the presence of strong, characteristic footprints in the same DMS-treated DNA samples at the two CBF1 sites of the LMP2A-promoter. Our in vivo results suggest a minor role for DNA methylation, while a more important role for histone acetylation in the regulation of EBV-induced CD23 expression. Furthermore, our in vivo footprinting results support the complex model of CD23 induction by EBV, rather than a simple model with direct transactivation of CD23 by EBNA-2.
authors.affiliation: Microbiological Research Group, National Center for Epidemiology, Pihenő út 1, H-1529 Budapest, Hungary.
authors.forename: Kalman
authors.initials: K
authors.lastname: Szenthe
authors.forename: Anita
authors.initials: A
authors.lastname: Koroknai
authors.forename: Ferenc
authors.initials: F
authors.lastname: Banati
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Bathori
authors.forename: Hans Helmut
authors.initials: HH
authors.lastname: Niller
authors.forename: Hans
authors.initials: H
authors.lastname: Wolf
authors.forename: Noemi
authors.initials: N
authors.lastname: Nagy
authors.forename: Eva
authors.initials: E
authors.lastname: Klein
authors.forename: Janos
authors.initials: J
authors.lastname: Minarovits
authors.forename: Daniel
authors.initials: D
authors.lastname: Salamon
mesh_terms: D000107:Acetylation; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D015151:Immunoblotting; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D011485:Protein Binding; D017455:Receptors, IgE / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D006657:Histones; D017455:Receptors, IgE; D014764:Viral Proteins