The Epstein–Barr virus nuclear antigen-1 reprograms transcription by mimicry of high mobility group A proteins

Giuseppe Coppotelli; Nouman Mughal; Simone Callegari; Ramakrishna Sompallae; Laia Caja; Martijn S. Luijsterburg; Nico P. Dantuma; Aristidis Moustakas; Maria G. Masucci

doi:10.1093/nar/gkt032

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The Epstein–Barr virus nuclear antigen-1 reprograms transcription by mimicry of high mobility group A proteins

Journal article

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The Epstein–Barr virus nuclear antigen-1 reprograms transcription by mimicry of high mobility group A proteins

Giuseppe Coppotelli, Nouman Mughal, Simone Callegari, Ramakrishna Sompallae, Laia Caja, Martijn S. Luijsterburg, Nico P. Dantuma, Aristidis Moustakas and Maria G. Masucci

Nucleic acids research, Vol.41(5), pp.2950-2962

03/01/2013

DOI: 10.1093/nar/gkt032

PMCID: PMC3597695

PMID: 23358825

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Abstract

Viral proteins reprogram their host cells by hijacking regulatory components of protein networks. Here we describe a novel property of the Epstein–Barr virus (EBV) nuclear antigen-1 (EBNA1) that may underlie the capacity of the virus to promote a global remodeling of chromatin architecture and cellular transcription. We found that the expression of EBNA1 in transfected human and mouse cells is associated with decreased prevalence of heterochromatin foci, enhanced accessibility of cellular DNA to micrococcal nuclease digestion and decreased average length of nucleosome repeats, suggesting de-protection of the nucleosome linker regions. This is a direct effect of EBNA1 because targeting the viral protein to heterochromatin promotes large-scale chromatin decondensation with slow kinetics and independent of the recruitment of adenosine triphosphate–dependent chromatin remodelers. The remodeling function is mediated by a bipartite Gly-Arg rich domain of EBNA1 that resembles the AT-hook of High Mobility Group A (HMGA) architectural transcription factors. Similar to HMGAs, EBNA1 is highly mobile in interphase nuclei and promotes the mobility of linker histone H1, which counteracts chromatin condensation and alters the transcription of numerous cellular genes. Thus, by regulating chromatin compaction, EBNA1 may reset cellular transcription during infection and prime the infected cells for malignant transformation.

Gene Regulation, Chromatin and Epigenetics

Details

Title: Subtitle: The Epstein–Barr virus nuclear antigen-1 reprograms transcription by mimicry of high mobility group A proteins
Creators: Giuseppe Coppotelli - Science for Life Laboratory
Nouman Mughal - Science for Life Laboratory
Simone Callegari - Karolinska Institutet
Ramakrishna Sompallae - Science for Life Laboratory
Laia Caja - Science for Life Laboratory
Martijn S. Luijsterburg - Science for Life Laboratory
Nico P. Dantuma - Science for Life Laboratory
Aristidis Moustakas - Science for Life Laboratory
Maria G. Masucci - Karolinska Institutet
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.41(5), pp.2950-2962
DOI: 10.1093/nar/gkt032
PMID: 23358825
PMCID: PMC3597695
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Publisher: Oxford University Press
Language: English
Date published: 03/01/2013
Academic Unit: Pathology
Record Identifier: 9984622055102771

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