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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/126387
Epstein–Barr virus-mediated transformation of B cells induces global chromatin changes independent to the acquisition of proliferation
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Epstein-Barr virus (EBV) infects and transforms human primary B cells inducing indefinite proliferation. To investigate the potential participation of chromatin mechanisms during the EBV-mediated transformation of resting B cells we performed an analysis of global changes in histone modifications. We observed a remarkable decrease and redistribution of heterochromatin marks including H4K20me3, H3K27me3 and H3K9me3. Loss of H4K20me3 and H3K9me3 occurred at constitutive heterochromatin repeats. For H3K27me3 and H3K9me3, comparison of ChIP-seq data revealed a decrease in these marks in thousands of genes, including clusters of HOX and ZNF genes, respectively. Moreover, DNase-seq data comparison between resting and EBV-transformed B cells revealed increased endonuclease accessibility in thousands of genomic sites. We observed that both loss of H3K27me3 and increased accessibility are associated with transcriptional activation. These changes only occurred in B cells transformed with EBV and not in those stimulated to proliferate with CD40L/IL-4, despite their similarities in the cell pathways involved and proliferation rates. In fact, B cells infected with EBNA-2 deficient EBV, which have much lower proliferation rates, displayed similar decreases for heterochromatic histone marks. Our study describes a novel phenomenon related to transformation of B cells, and highlights its independence of the pure acquisition of proliferation.
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HERNANDO, Henar, ISLAM, Abul b. m. m. k., RODRÍGUEZ UBREVA, Javier, FORNÉ, Ignasi, CIUDAD, Laura, IMHOF, Axel, SHANNON-LOWE, Claire, BALLESTAR TARÍN, Esteban. Epstein–Barr virus-mediated transformation of B cells induces global chromatin changes independent to the acquisition of proliferation. _Nucleic Acids Research_. 2014. Vol. 42, núm. 1, pàgs. 249-263. [consulta: 20 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/126387]