TY - JOUR
T1 - Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation
AU - Vilarrasa-Blasi, Roser
AU - Soler-Vila, Paula
AU - Verdaguer-Dot, Núria
AU - Russiñol, Núria
AU - Di Stefano, Marco
AU - Chapaprieta, Vicente
AU - Clot, Guillem
AU - Farabella, Irene
AU - Cuscó, Pol
AU - Kulis, Marta
AU - Agirre, Xabier
AU - Prosper, Felipe
AU - Beekman, Renée
AU - Beà, Silvia
AU - Colomer, Dolors
AU - Stunnenberg, Hendrik G.
AU - Gut, Ivo
AU - Campo, Elias
AU - Marti-Renom, Marc A.
AU - Martin-Subero, José Ignacio
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85100029224
U2 - 10.1038/s41467-020-20849-y
DO - 10.1038/s41467-020-20849-y
M3 - Article
C2 - 33510161
AN - SCOPUS:85100029224
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 651
ER -