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PMID: 28968461 Published · epublish English Journal Article

EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells.

PLoS pathogens ·Vol. 13 ·No. 10 ·2017-10-00 ·Pages e1006664

Glaser LV, Rieger S, Thumann S, Beer S, Kuklik-Roos C, Martin DE, Maier KC, Harth-Hertle ML, Grüning B, Backofen R, Krebs S, Blum H, Zimmer R, Erhard F, Kempkes B

Abstract

Epstein-Barr virus (EBV) infection converts resting human B cells into permanently proliferating lymphoblastoid cell lines (LCLs). The Epstein-Barr virus nuclear antigen 2 (EBNA2) plays a key role in this process. It preferentially binds to B cell enhancers and establishes a specific viral and cellular gene expression program in LCLs. The cellular DNA binding factor CBF1/CSL serves as a sequence specific chromatin anchor for EBNA2. The ubiquitous expression of this highly conserved protein raises the question whether additional cellular factors might determine EBNA2 chromatin binding selectively in B cells. Here we used CBF1 deficient B cells to identify cellular genes up or downregulated by EBNA2 as well as CBF1 independent EBNA2 chromatin binding sites. Apparently, CBF1 independent EBNA2 target genes and chromatin binding sites can be identified but are less frequent than CBF1 dependent EBNA2 functions. CBF1 independent EBNA2 binding sites are highly enriched for EBF1 binding motifs. We show that EBNA2 binds to EBF1 via its N-terminal domain. CBF1 proficient and deficient B cells require EBF1 to bind to CBF1 independent binding sites. Our results identify EBF1 as a co-factor of EBNA2 which conveys B cell specificity to EBNA2.

MeSH Terms
B-Lymphocytes/metabolism,virology Cell Line Chromatin/metabolism Epstein-Barr Virus Nuclear Antigens/metabolism Herpesvirus 4, Human/metabolism Humans Promoter Regions, Genetic/immunology Protein Binding Regulatory Sequences, Nucleic Acid/immunology Trans-Activators/metabolism Viral Proteins/metabolism
Chemicals
Chromatin EBF1 protein, human EBNA-2 protein, Human herpesvirus 4 Epstein-Barr Virus Nuclear Antigens Trans-Activators Viral Proteins
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Glaser Laura V
Department of Gene Vectors, Helmholtz Center Munich, Munich, Germany.
Rieger Simone ORCID
Department of Gene Vectors, Helmholtz Center Munich, Munich, Germany.
Thumann Sybille
Department of Gene Vectors, Helmholtz Center Munich, Munich, Germany.
Beer Sophie
Department of Gene Vectors, Helmholtz Center Munich, Munich, Germany.
Kuklik-Roos Cornelia
Department of Gene Vectors, Helmholtz Center Munich, Munich, Germany.
Martin Dietmar E
Gene Center, Ludwig-Maximilians-University, Munich, Germany.
Maier Kerstin C
Gene Center, Ludwig-Maximilians-University, Munich, Germany.
Harth-Hertle Marie L ORCID
Department of Gene Vectors, Helmholtz Center Munich, Munich, Germany.
Grüning Björn ORCID
Bioinformatics, Institute for Informatics, Albert-Ludwigs-University, Freiburg, Germany.
Backofen Rolf ORCID
Bioinformatics, Institute for Informatics, Albert-Ludwigs-University, Freiburg, Germany.
Krebs Stefan
Gene Center, Ludwig-Maximilians-University, Munich, Germany.
Blum Helmut
Gene Center, Ludwig-Maximilians-University, Munich, Germany.
Zimmer Ralf ORCID
Teaching and Research Unit Bioinformatics, Institute of Informatics, Ludwig-Maximilians-University, Munich, Germany.
Erhard Florian ORCID
Teaching and Research Unit Bioinformatics, Institute of Informatics, Ludwig-Maximilians-University, Munich, Germany.
Kempkes Bettina ORCID
Department of Gene Vectors, Helmholtz Center Munich, Munich, Germany.
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Article Info
Journal
PLoS pathogens
Abbr.
PLoS Pathog
ISSN
1553-7374
DOI
10.1371/journal.ppat.1006664
Published
2017-10-00
Epub
2017-00-02
Pages
e1006664
Language
English
Region
United States
NLM ID
101238921
PMCID
PMC5638620
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.ppat.1006664 PMC Full Text View journal details
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