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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Viral oncogene EBNALP regulates YY1 DNA binding and alters host 3D genome organization.
EMBO Rep. 26, 810-835 (2025)
Verlagsversion
Forschungsdaten
DOI
PMC
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
ISSN (print) / ISBN
1469-221X
e-ISSN
1469-3178
Zeitschrift
EMBO Reports
Quellenangaben
Band: 26,
Heft: 3,
Seiten: 810-835
Verlag
EMBO Press
Verlagsort
Campus, 4 Crinan St, London, N1 9xw, England
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Research Unit Gene Vector (AGV)
Förderungen
Fund to Sustain Research Excellence from Brigham Research Institute
NIH
HHS | NIH | National Institute of Dental and Craniofacial Research (NIDR)
NIH
HHS | NIH | National Institute of Dental and Craniofacial Research (NIDR)