Identifying sites bound by Epstein-Barr virus nuclear antigen 1 (EBNA1) in the human genome: defining a position-weighted matrix to predict sites bound by EBNA1 in viral genomes

J Virol. 2009 Apr;83(7):2930-40. doi: 10.1128/JVI.01974-08. Epub 2009 Jan 7.

Abstract

We identified binding sites for Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) in the human genome using chromatin immunoprecipitation and microarrays. The sequences for these newly identified sites were used to generate a position-weighted matrix (PWM) for EBNA1's DNA-binding sites. This PWM helped identify additional DNA-binding sites for EBNA1 in the genomes of EBV, Kaposi's sarcoma-associated herpesvirus, and cercopithecine herpesvirus 15 (CeHV-15) (also called herpesvirus papio 15). In particular, a homologue of the Rep* locus in EBV was predicted in the genome of CeHV-15, which is notable because Rep* of EBV was not predicted by the previously developed consensus sequence for EBNA1's binding DNA. The Rep* of CeHV-15 functions as an origin of DNA synthesis in the EBV-positive cell line Raji; this finding thus builds on a set of DNA-binding sites for EBNA1 predicted in silico.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • Chromatin Immunoprecipitation
  • DNA / metabolism*
  • DNA, Viral / metabolism*
  • Epstein-Barr Virus Nuclear Antigens / metabolism*
  • Genome, Human
  • Genome, Viral
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / physiology*
  • Herpesvirus 8, Human / genetics
  • Humans
  • Protein Array Analysis
  • Protein Binding
  • Virus Replication*

Substances

  • DNA, Viral
  • Epstein-Barr Virus Nuclear Antigens
  • DNA
  • EBV-encoded nuclear antigen 1