EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells.
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 cellu...
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2017-10-01
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Series: | PLoS Pathogens |
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doaj-9ead8bedc269442990447aa13ffbca212020-11-25T02:20:16ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742017-10-011310e100666410.1371/journal.ppat.1006664EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells.Laura V GlaserSimone RiegerSybille ThumannSophie BeerCornelia Kuklik-RoosDietmar E MartinKerstin C MaierMarie L Harth-HertleBjörn GrüningRolf BackofenStefan KrebsHelmut BlumRalf ZimmerFlorian ErhardBettina KempkesEpstein-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.http://europepmc.org/articles/PMC5638620?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laura V Glaser Simone Rieger Sybille Thumann Sophie Beer Cornelia Kuklik-Roos Dietmar E Martin Kerstin C Maier Marie L Harth-Hertle Björn Grüning Rolf Backofen Stefan Krebs Helmut Blum Ralf Zimmer Florian Erhard Bettina Kempkes |
spellingShingle |
Laura V Glaser Simone Rieger Sybille Thumann Sophie Beer Cornelia Kuklik-Roos Dietmar E Martin Kerstin C Maier Marie L Harth-Hertle Björn Grüning Rolf Backofen Stefan Krebs Helmut Blum Ralf Zimmer Florian Erhard Bettina Kempkes EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells. PLoS Pathogens |
author_facet |
Laura V Glaser Simone Rieger Sybille Thumann Sophie Beer Cornelia Kuklik-Roos Dietmar E Martin Kerstin C Maier Marie L Harth-Hertle Björn Grüning Rolf Backofen Stefan Krebs Helmut Blum Ralf Zimmer Florian Erhard Bettina Kempkes |
author_sort |
Laura V Glaser |
title |
EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells. |
title_short |
EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells. |
title_full |
EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells. |
title_fullStr |
EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells. |
title_full_unstemmed |
EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells. |
title_sort |
ebf1 binds to ebna2 and promotes the assembly of ebna2 chromatin complexes in b cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2017-10-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC5638620?pdf=render |
work_keys_str_mv |
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