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

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 a...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844026/
https://www.ncbi.nlm.nih.gov/pubmed/33510161
http://dx.doi.org/10.1038/s41467-020-20849-y
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author 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
author_facet 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
author_sort Vilarrasa-Blasi, Roser
collection PubMed
description 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.
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spelling pubmed-78440262021-02-08 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, 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 Nat Commun Article 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. Nature Publishing Group UK 2021-01-28 /pmc/articles/PMC7844026/ /pubmed/33510161 http://dx.doi.org/10.1038/s41467-020-20849-y Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation
title Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation
title_full Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation
title_fullStr Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation
title_full_unstemmed Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation
title_short Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation
title_sort dynamics of genome architecture and chromatin function during human b cell differentiation and neoplastic transformation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844026/
https://www.ncbi.nlm.nih.gov/pubmed/33510161
http://dx.doi.org/10.1038/s41467-020-20849-y
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