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

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-01-02 DOI:10.1038/s44319-024-00357-6

Chong Wang, Merrin Manlong Leong, Weiyue Ding, Yohei Narita, Xiang Liu, Hongbo Wang, Stefanie P T Yiu, Jessica Lee, Katelyn R S Zhao, Amy Cui, Benjamin Gewurz, Wolfgang Hammerschmidt, Mingxiang Teng, Bo Zhao

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引用次数: 0

Abstract

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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病毒癌基因EBNALP调节YY1 DNA结合并改变宿主三维基因组组织。

eb病毒（EBV）核抗原前导蛋白（ebalp）对幼稚B淋巴细胞（NBLs）的永生化至关重要。然而，其机制仍然难以捉摸。为了了解EBNALP在b细胞转化中的作用，我们使用多组学技术比较了感染野生型EBV和EBNALP缺失突变型EBV的NBLs。EBNALP失活改变了增强子-启动子相互作用，导致CCND2降低，CASP1和BCL2L11表达增加。在机制上，EBNALP与循环因子YY1相互作用并共定位。EBNALP的缺失减少了YY1 dna结合和增强子-启动子相互作用，与YY1缺失所观察到的效果相似。此外，EBNALP与DPF2共定位，DPF2是一种结合H3K14ac和H4K16ac的蛋白质。CRISPR缺失DPF2会降低EBNALP和YY1的DNA结合，这表明DPF2/EBNALP复合物可能将YY1与DNA连接起来，从而增加增强子-启动子的相互作用。EBNALP失活还增加了CASP1和BCL2L11位点的增强子-启动子相互作用，以及DPF2和YY1结合和DNA可及性升高。我们的数据表明，EBNALP调节YY1重新连接宿主基因组，这可能促进幼稚b细胞转化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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