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Vilarrasa-Blasi, Roser; Soler-Vila, Paula; Verdaguer-Dot, Núria; Russiñol, Núria; Di Stefano, Marco; Chapaprieta, Vicente; Clot, Guillem; Farabella, Irene; Cuscó, Pol; Kulis, Marta; Agirre, Xabier; Prosper, Felipe; Beekman, Renée; Beà, Silvia; Colomer, Dolors; Stunnenberg, Hendrik G; Gut, Ivo; Campo, Elias; Marti-Renom, Marc A; Martin-Subero, José Ignacio
Nature communications, 01/2021, Letnik: 12, Številka: 1Journal Article
To investigate the three-dimensional (3D) genome architecture across normal B cell differentiation and in neoplastic cells from different subtypes of chronic lymphocytic leukemia and mantle cell lymphoma patients, here we integrate in situ Hi-C and nine additional omics layers. Beyond conventional active (A) and inactive (B) compartments, we uncover a highly-dynamic intermediate compartment enriched in poised and polycomb-repressed chromatin. During B cell development, 28% of the compartments change, mostly involving a widespread chromatin activation from naive to germinal center B cells and a reversal to the naive state upon further maturation into memory B cells. B cell neoplasms are characterized by both entity and subtype-specific alterations in 3D genome organization, including large chromatin blocks spanning key disease-specific genes. This study indicates that 3D genome interactions are extensively modulated during normal B cell differentiation and that the genome of B cell neoplasias acquires a tumor-specific 3D genome architecture.
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in: SICRIS
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