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

Roser Vilarrasa-Blasi, Paula Soler-Vila, Núria Verdaguer-Dot, Núria Russiñol, Marco Stefano, Vicente Chapaprieta, Guillem Clot, Irene Farabella, Pol Cuscó, Marta Kulis, Xabier Agirre, Felipe Prosper, Renée Beekman, Silvia Beà, Dolors Colomer, Hendrik G. Stunnenberg, Ivo Gut, Elias Campo, Marc A. Marti-Renom () and José Ignacio Martin-Subero ()
Additional contact information
Roser Vilarrasa-Blasi: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Paula Soler-Vila: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
Núria Verdaguer-Dot: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Núria Russiñol: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Marco Stefano: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
Vicente Chapaprieta: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Guillem Clot: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Irene Farabella: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
Pol Cuscó: Gastrointestinal and Endocrine Tumors Group, Vall d’Hebron Institute of Oncology (VHIO)
Marta Kulis: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Xabier Agirre: Centro de Investigación Biomédica en Red de Cáncer (CIBERONC)
Felipe Prosper: Centro de Investigación Biomédica en Red de Cáncer (CIBERONC)
Renée Beekman: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Silvia Beà: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Dolors Colomer: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Hendrik G. Stunnenberg: Radboud University
Ivo Gut: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
Elias Campo: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Marc A. Marti-Renom: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
José Ignacio Martin-Subero: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20849-y

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DOI: 10.1038/s41467-020-20849-y

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