CTCF and Sp1 interact with the murine gammaherpesvirus 68 internal repeat elements

Hannah C. Stevens, Kevin S.W. Cham, David J. Hughes, Ren Sun, Jeffery T. Sample, Vivien J. Bubb, James P. Stewart, John P. Quinn

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Herpesviruses maintain a dynamic balance between latency and productive infection. This is a complex process regulated by viral and cellular factors. We have developed a Murine gammaherpesvirus 68 (MHV-68) model system in which to study mechanisms underlying balance between latency and lytic infection. We have generated an epithelial cell line that carries MHV-68 in a tightly latent form by using a bacterial artificial chromosome clone of the virus genome with a mutation in the MHV-68 major lytic R transactivator gene. Complementation of this defect in trans by transfection with a plasmid encoding R transactivator initiated and restored the productive cycle. This cell line model was used to investigate transcription factor occupancy (CCCTC binding factor [CTCF] and Sp1) of the two internal repeat elements in the viral genome during latency and reactivation using chromatin immunoprecipitation. Our results show that CTCF can bind to the 40-bp and the 100-bp repeat sequences during latency, whereas binding is reduced upon reactivation. In contrast, Sp1 only bound to the 100-bp repeat after reactivation. Our results indicate that the large internal repeat sequences in MHV-68 have different functions. We hypothesise that the 40-bp repeat may be involved in regulation of gene expression during the maintenance of latency, while the 100-bp repeat domain may be involved in regulation of the lytic cycle.

Original languageEnglish (US)
Pages (from-to)265-273
Number of pages9
JournalVirus Genes
Volume45
Issue number2
DOIs
StatePublished - Oct 1 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Virology

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    Stevens, H. C., Cham, K. S. W., Hughes, D. J., Sun, R., Sample, J. T., Bubb, V. J., Stewart, J. P., & Quinn, J. P. (2012). CTCF and Sp1 interact with the murine gammaherpesvirus 68 internal repeat elements. Virus Genes, 45(2), 265-273. https://doi.org/10.1007/s11262-012-0769-y