Contributions of CTCF and DNA methyltransferases DNMT1 and DNMT3B to Epstein-Barr virus restricted latency

David J. Hughes, Elessa M. Marendy, Carol A. Dickerson, Kristen D. Yetming, Clare Sample, Jeffery Sample

Research output: Contribution to journalArticle

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Abstract

Establishment of persistent Epstein-Barr virus (EBV) infection requires transition from a program of full viral latency gene expression (latency III) to one that is highly restricted (latency I and 0) within memory B lymphocytes. It is well established that DNA methylation plays a critical role in EBV gene silencing, and recently the chromatin boundary protein CTCF has been implicated as a pivotal regulator of latency via its binding to several loci within the EBV genome. One notable site is upstream of the common EBNA gene promoter Cp, at which CTCF may act as an enhancer-blocking factor to initiate and maintain silencing of EBNA gene transcription. It was previously suggested that increased expression of CTCF may underlie its potential to promote restricted latency, and here we also noted elevated levels of DNA methyltransferase 1 (DNMT1) and DNMT3B associated with latency I. Within B-cell lines that maintain latency I, however, stable knockdown of CTCF, DNMT1, or DNMT3B or of DNMT1 and DNMT3B in combination did not result in activation of latency III protein expression or EBNA gene transcription, nor did knockdown of DNMTs significantly alter CpG methylation within Cp. Thus, differential expression of CTCF and DNMT1 and -3B is not critical for maintenance of restricted latency. Finally, mutant EBV lacking the Cp CTCF binding site exhibited sustained Cp activity relative to wild-type EBV in a recently developed B-cell superinfection model but ultimately was able to transition to latency I, suggesting that CTCF contributes to but is not necessarily essential for the establishment of restricted latency.

Original languageEnglish (US)
Pages (from-to)1034-1045
Number of pages12
JournalJournal of Virology
Volume86
Issue number2
DOIs
StatePublished - Jan 1 2012

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Virus Latency
Human herpesvirus 4
methyltransferases
Methyltransferases
Human Herpesvirus 4
B-Lymphocytes
DNA
B-lymphocytes
Gene Silencing
gene silencing
Superinfection
transcription (genetics)
Epstein-Barr Virus Infections
Viral Genes
DNA Methylation
Methylation
Genes
Chromatin
DNA methylation
methylation

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Hughes, David J. ; Marendy, Elessa M. ; Dickerson, Carol A. ; Yetming, Kristen D. ; Sample, Clare ; Sample, Jeffery. / Contributions of CTCF and DNA methyltransferases DNMT1 and DNMT3B to Epstein-Barr virus restricted latency. In: Journal of Virology. 2012 ; Vol. 86, No. 2. pp. 1034-1045.
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Contributions of CTCF and DNA methyltransferases DNMT1 and DNMT3B to Epstein-Barr virus restricted latency. / Hughes, David J.; Marendy, Elessa M.; Dickerson, Carol A.; Yetming, Kristen D.; Sample, Clare; Sample, Jeffery.

In: Journal of Virology, Vol. 86, No. 2, 01.01.2012, p. 1034-1045.

Research output: Contribution to journalArticle

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