Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation

Vilarrasa-Blasi, Roser; Soler-Vila, Paula; Verdaguer-Dot, Núria; Russiñol, Núria; Di Stefano, Marco; Chapaprieta, Vicente; Clot, Guillem; Farabella, Irene; Cuscó Pons, Pol, 1987-; Kulis, Marta; Agirre, Xabier; Prosper, Felipe; Beekman, Renée; Beà, Sílvia; Colomer Pujol, Dolors; Stunnenberg, Hendrik G.; Gut, Ivo Glynne; Campo, Elias; Marti-Renom, Marc A.; Martin-Subero, José Ignacio

doi:http://dx.doi.org/10.1038/s41467-020-20849-y

Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation

Citation

Vilarrasa-Blasi R, Soler-Vila P, Verdaguer-Dot N, Russiñol N, Di Stefano M, Chapaprieta V et al. Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation. Nat Commun. 2021 Jan 28; 12(1): 651. DOI: 10.1038/s41467-020-20849-y

Abstract

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.