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?

URN to cite this document:

urn:nbn:de:bvb:355-epub-416645 Copy

DOI to cite this document:

10.5283/epub.41664 Copy

Niller, Hans Helmut ; Minarovits, Janos

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License: Creative Commons Attribution Non-commercial Share Alike 3.0 PDF - Published Version (320kB)

Date of publication of this fulltext: 20 Feb 2020 07:21

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Details

Item type:	Article
Journal or Publication Title:	Pathogens
Publisher:	Molecular Diversity Preservation International (MDPI)
Volume:	1
Page Range:	pp. 37-51
Date:	2012
Institutions:	Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Identification Number:	Value Type 10.3390/pathogens1010037 DOI
Keywords:	DNA-looping; CpG-methylation; histone; chromatin; oriP
Dewey Decimal Classification:	600 Technology > 610 Medical sciences Medicine
Status:	Published
Refereed:	Yes, this version has been refereed
Created at the University of Regensburg:	Yes
Item ID:	41664

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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, ...

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.

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Metadata last modified: 29 Sep 2021 07:41

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