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Wang, C.* ; Leong, M.M.* ; Ding, W.* ; Narita, Y.* ; Liu, X.* ; Wang, H.* ; Yiu, S.P.T.* ; Lee, J.* ; Zhao, K.R.S.* ; Cui, A.* ; Gewurz, B.* ; Hammerschmidt, W. ; Teng, M.* ; Zhao, B.*

Viral oncogene EBNALP regulates YY1 DNA binding and alters host 3D genome organization.

EMBO Rep. 26, 810-835 (2025)
Verlagsversion Forschungsdaten DOI PMC
Creative Commons Lizenzvertrag
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNALP) is essential for the immortalization of naive B lymphocytes (NBLs). However, the mechanisms remain elusive. To understand EBNALP's role in B-cell transformation, we compare NBLs infected with wild-type EBV and an EBNALP-null mutant EBV using multi-omics techniques. EBNALP inactivation alters enhancer-promoter interactions, resulting in decreased CCND2 and increased CASP1 and BCL2L11 expression. Mechanistically, EBNALP interacts with and colocalizes with the looping factor YY1. Depletion of EBNALP reduces YY1 DNA-binding and enhancer-promoter interactions, similar to effects observed with YY1 depletion. Furthermore, EBNALP colocalizes with DPF2, a protein that binds to H3K14ac and H4K16ac. CRISPR depletion of DPF2 reduces both EBNALP and YY1 DNA binding, suggesting that the DPF2/EBNALP complex may tether YY1 to DNA to increase enhancer-promoter interactions. EBNALP inactivation also increases enhancer-promoter interactions at the CASP1 and BCL2L11 loci, along with elevated DPF2 and YY1 binding and DNA accessibility. Our data suggest that EBNALP regulates YY1 to rewire the host genome, which might facilitate naive B-cell transformation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 3d Genome Organization ; Ebnalp ; Epstein–barr Virus ; Hichip ; Yy1; Epstein-barr-virus; Transcription Factor Yy1; Gene-expression; Protein Lp; C-myc; Promoter; Leader; Domain; Repression; Ctcf
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Zeitschrift EMBO Reports
Quellenangaben Band: 26, Heft: 3, Seiten: 810-835 Artikelnummer: , Supplement: ,
Verlag EMBO Press
Verlagsort Campus, 4 Crinan St, London, N1 9xw, England
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501500-001
Förderungen Fund to Sustain Research Excellence from Brigham Research Institute
NIH
HHS | NIH | National Institute of Dental and Craniofacial Research (NIDR)
DOI 10.1038/s44319-024-00357-6
WOS ID 001388171700001
Scopus ID 85213974796
PubMed ID 39747661
Erfassungsdatum 2025-03-18
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