Premium
Molecular network of chromatin immunoprecipitation followed by deep sequencing‐based (ChIP‐Seq) E pstein– B arr virus nuclear antigen 1‐target cellular genes supports biological implications of E pstein– B arr virus persistence in multiple sclerosis
Author(s) -
Satoh Junichi,
Kawatsuki,
Yamamoto Yoji
Publication year - 2013
Publication title -
clinical and experimental neuroimmunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.297
H-Index - 15
ISSN - 1759-1961
DOI - 10.1111/cen3.12035
Subject(s) - biology , chromatin immunoprecipitation , gene , virus latency , chromatin , virus , viral replication , virology , genetics , gene expression , promoter
Objectives Epstein– B arr virus ( EBV ) infection confers a strong risk factor for development of multiple sclerosis ( MS ). EBV preferentially infects B lymphocytes to establish a life‐long latent infection. EBV nuclear antigen 1 ( EBNA 1), acting as a transcriptional activator, plays a central role in the replication and maintenance of the latent episomal EBV genome in EBV ‐infected host cells. However, the comprehensive set of host cellular genes directly regulated by EBNA 1 relevant to the immunopathogenesis of MS remains to be elucidated. Methods We investigated the chromatin immunoprecipitation followed by deep sequencing (ChIP‐Seq) dataset of R aji cells, an EBV ‐positive B urkitt's lymphoma cell line. We studied the molecular network of target genes by pathway analysis tools of bioinformatics. Results We identified the set of 228 EBNA 1‐target cellular genes. The EBNA 1‐binding sites were located mainly in intronic regions of target genes with an existence of the palindromic consensus sequence motif. By pathway analysis using Ingenuity Pathways Analysis and K ey M olnet, the EBNA 1‐target cellular gene network showed a significant relationship with the networks related to cell death and survival, and transcriptional regulation by interferon‐regulatory factor (IRF), and signal transducer and activator of transcription (STAT). Conclusions These results show that the EBNA 1‐target cellular gene network is closely associated with maintenance of EBV persistence by controlling the fate of EBV ‐infected host cells, and by aberrantly regulating the production of host‐derived antiviral interferons and other cytokines, supporting biological implications of EBV persistence in MS .