Detalle Publicación

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

Autores: Vilarrasa-Blasi, R.; Soler-Vila, P.; Verdaguer-Dot, N.; Russinol, N.; Di Stefano, M.; Chapaprieta, V.; Clot, G.; Farabella, I.; Cusco, P.; Kulis, M.; Aguirre Ena, Xabier; Prosper Cardoso, Felipe; Beekman, R.; Bea, S.; Colomer, D.; Stunnenberg, H. G.; Gut, I.; Campo, E.; Marti-Renom, M. A.; Martin-Subero, J. I. (Autor de correspondencia)
Título de la revista: NATURE COMMUNICATIONS
ISSN: 2041-1723
Volumen: 12
Número: 1
Fecha de publicación: 2021
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.