tailieunhanh - Báo cáo y học: " Genome-wide analysis of host-chromosome binding sites for Epstein-Barr Virus Nuclear Antigen 1 (EBNA1)"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Genome-wide analysis of host-chromosome binding sites for Epstein-Barr Virus Nuclear Antigen 1 (EBNA1) | Lu et al. Virology Journal 2010 7 262 http content 7 1 262 VIROLOGY JOURNAL RESEARCH Open Access Genome-wide analysis of host-chromosome binding sites for Epstein-Barr Virus Nuclear Antigen 1 EBNA1 1 1 1 1 1 1 Fang Lu Priyankara Wikramasinghe Julie Norseen Kevin Tsai Pu Wang Louise Showe Ramana V Davuluri Paul M Lieberman1 Abstract The Epstein-Barr Virus EBV Nuclear Antigen 1 EBNA1 protein is required for the establishment of EBV latent infection in proliferating B-lymphocytes. EBNA1 is a multifunctional DNA-binding protein that stimulates DNA replication at the viral origin of plasmid replication OriP regulates transcription of viral and cellular genes and tethers the viral episome to the cellular chromosome. EBNA1 also provides a survival function to B-lymphocytes potentially through its ability to alter cellular gene expression. To better understand these various functions of EBNA1 we performed a genome-wide analysis of the viral and cellular DNA sites associated with EBNA1 protein in a latently infected Burkitt lymphoma B-cell line. Chromatin-immunoprecipitation ChIP combined with massively parallel deep-sequencing ChIP-Seq was used to identify cellular sites bound by EBNA1. Sites identified by ChIP-Seq were validated by conventional real-time PCR and ChIP-Seq provided quantitative high-resolution detection of the known EBNA1 binding sites on the EBV genome at OriP and Qp. We identified at least one cluster of unusually high-affinity EBNA1 binding sites on chromosome 11 between the divergent FAM55 D and FAM55B genes. A consensus for all cellular EBNA1 binding sites is distinct from those derived from the known viral binding sites suggesting that some of these sites are indirectly bound by EBNA1. EBNA1 also bound close to the transcriptional start sites of a large number of cellular genes including HDAC3 CDC7 and MAP3K1 which we show are positively regulated by EBNA1. EBNA1 binding sites were enriched in some repetitive elements especially