Scientific publications
Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation. Scientific Publication
Roser Vilarrasa-Blasi # 1 2, Paula Soler-Vila # 3, Núria Verdaguer-Dot 1, Núria Russiñol 1, Marco Di Stefano 3, Vicente Chapaprieta 1, Guillem Clot 1 4, Irene Farabella 3, Pol Cuscó 5, Marta Kulis 1, Xabier Agirre 4 6, Felipe Prosper 4 6 7, Renée Beekman 1, Silvia Beà 1 4, Dolors Colomer 1 4 8, Hendrik G Stunnenberg 9, Ivo Gut 3 10, Elias Campo 1 2 4, Marc A Marti-Renom 11 12 13 14, José Ignacio Martin-Subero 15 16 17 18
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.
CITATION Nat Commun. 2021 Jan 28;12(1):651. doi: 10.1038/s41467-020-20849-y.
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