Pathogens 2012, 1(1), 37-51; doi:10.3390/pathogens1010037
Review

Similarities between the Epstein-Barr Virus (EBV) Nuclear Protein EBNA1 and the Pioneer Transcription Factor FoxA: Is EBNA1 a “Bookmarking” Oncoprotein that Alters the Host Cell Epigenotype?

1 Institute for Medical Microbiology and Hygiene, University of Regensburg, Franz-Josef-Strauß Allee 11, Regensburg D-93053, Germany 2 Microbiological Research Group, National Center for Epidemiology, Piheno u. 1., Budapest H-1529, Hungary
* Author to whom correspondence should be addressed.
Received: 2 August 2012; in revised form: 21 August 2012 / Accepted: 4 September 2012 / Published: 17 September 2012
(This article belongs to the Special Issue Infection and Cancer)
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Abstract: EBNA1, a nuclear protein expressed in all EBV-associated neoplasms is indispensable for the maintenance of the viral episomes in latently infected cells. EBNA1 may induce genetic alterations by upregulating cellular recombinases, production of reactive oxygen species (ROS) and affecting p53 levels and function. All these changes may contribute to tumorigenesis. In this overview we focus, however, on the epigenetic alterations elicited by EBNA1 by drawing a parallel between EBNA1 and the FoxA family of pioneer transcription factors. Both EBNA1 and FoxA induce local DNA demethylation, nucleosome destabilization and bind to mitotic chromosomes. Local DNA demethylation and nucleosome rearrangement mark active promoters and enhancers. In addition, EBNA1 and FoxA, when associated with mitotic chromatin may “bookmark” active genes and ensure their reactivation in postmitotic cells (epigenetic memory). We speculate that DNA looping induced by EBNA1-EBNA1 interactions may reorganize the cellular genome. Such chromatin loops, sustained in mitotic chromatin similarly to the long-distance interactions mediated by the insulator protein CTCF, may also mediate the epigenetic inheritance of gene expression patterns. We suggest that EBNA1 has the potential to induce patho-epigenetic alterations contributing to tumorigenesis.
Keywords: DNA-looping; CpG-methylation; histone; chromatin; oriP

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MDPI and ACS Style

Niller, H.H.; Minarovits, J. Similarities between the Epstein-Barr Virus (EBV) Nuclear Protein EBNA1 and the Pioneer Transcription Factor FoxA: Is EBNA1 a “Bookmarking” Oncoprotein that Alters the Host Cell Epigenotype? Pathogens 2012, 1, 37-51.

AMA Style

Niller HH, Minarovits J. Similarities between the Epstein-Barr Virus (EBV) Nuclear Protein EBNA1 and the Pioneer Transcription Factor FoxA: Is EBNA1 a “Bookmarking” Oncoprotein that Alters the Host Cell Epigenotype? Pathogens. 2012; 1(1):37-51.

Chicago/Turabian Style

Niller, Hans Helmut; Minarovits, Janos. 2012. "Similarities between the Epstein-Barr Virus (EBV) Nuclear Protein EBNA1 and the Pioneer Transcription Factor FoxA: Is EBNA1 a “Bookmarking” Oncoprotein that Alters the Host Cell Epigenotype?" Pathogens 1, no. 1: 37-51.

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