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

PLoS Pathogens

Rolf Backofen¹  Björn Grüning¹  Marie L. Harth-Hertle²  Cornelia Kuklik-Roos²  Simone Rieger²  Sybille Thumann²  Sophie Beer²  Bettina Kempkes²  Laura V. Glaser²  Kerstin C. Maier³  Stefan Krebs³  Helmut Blum³  Dietmar E. Martin³  Ralf Zimmer⁴  Florian Erhard⁴ 

[1] Bioinformatics, Institute for Informatics, Albert-Ludwigs-University, Freiburg, Germany;Department of Gene Vectors, Helmholtz Center Munich, Munich, Germany;Gene Center, Ludwig-Maximilians-University, Munich, Germany;Teaching and Research Unit Bioinformatics, Institute of Informatics, Ludwig-Maximilians-University, Munich, Germany

关键词: B cells;    Chromatin;    Cell binding;    Gene expression;    Transcription factors;    Gene regulation;    Estrogens;    Genomic signal processing;   

DOI  :  10.1371/journal.ppat.1006664

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY