EBNA leader protein orchestrates chromatin architecture remodeling during Epstein-Barr virus-induced B cell transformation
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Epstein-Barr virus Nuclear Antigen Leader Protein (EBNA-LP) plays a pivotal role in the transformation of B cells by Epstein-Barr virus (EBV), functioning independently of EBNA2 to regulate chromatin architecture and gene expression. Our study reveals that EBNA-LP binds to chromatin regions distinct from EBNA2 and facilitates the formation of long-distance chromatin loops by interacting with the cellular factor YY1. This interaction reconfigures the three-dimensional structure of the host genome, enhancing the integrity of topologically associating domains (TADs) and promoting the interaction between enhancers and promoters within these domains. In EBV-infected B cells, EBNA-LP strengthens YY1-mediated chromatin loops within TADs, which helps maintain stable regulatory programs essential for B cell transformation. Notably, EBNA-LP is crucial for establishing EBV-induced enhancers, yet it is not required for their maintenance once formed. Additionally, our data suggest a compensatory increase in CTCF binding in the absence of EBNA-LP, leading to more promiscuous chromatin interactions between TADs and a reduced TAD insulation at their boundaries. These findings provide new insights into the molecular mechanisms by which EBV reshapes the host genome chromatin architecture to support B cell transformation and highlight potential therapeutic targets for disrupting EBV-driven oncogenesis.
Date Issued
2025-07-08
Date Acceptance
2025-06-17
Citation
Nucleic Acids Research (NAR), 2025, 53 (12)
ISSN
0305-1048
Publisher
Oxford University Press
Journal / Book Title
Nucleic Acids Research (NAR)
Volume
53
Issue
12
Copyright Statement
© The Author(s) 2025. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40598900
PII: 8180743
Subjects
ACTIVATION
Biochemistry & Molecular Biology
DNA LOOPS
ENHANCERS
EXPRESSION
GENOME
Life Sciences & Biomedicine
LOCALIZATION
LP
REGULATOR
Science & Technology
TRANSCRIPTION FACTORS
YY1
Publication Status
Published
Coverage Spatial
England
Article Number
gkaf629
Date Publish Online
2025-07-02