Nature communications · 2021
Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation.
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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
Аннотация
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.