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Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation.
- Source :
-
Nature communications [Nat Commun] 2021 Jan 28; Vol. 12 (1), pp. 651. Date of Electronic Publication: 2021 Jan 28. - Publication Year :
- 2021
-
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.
- Subjects :
- B-Lymphocytes cytology
Gene Expression Regulation, Neoplastic
Genomics methods
Humans
Leukemia, Lymphocytic, Chronic, B-Cell genetics
Leukemia, Lymphocytic, Chronic, B-Cell pathology
Lymphoma, Mantle-Cell genetics
Lymphoma, Mantle-Cell pathology
B-Lymphocytes metabolism
Cell Differentiation genetics
Cell Transformation, Neoplastic genetics
Chromatin genetics
Chromatin Assembly and Disassembly genetics
Genome, Human genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 33510161
- Full Text :
- https://doi.org/10.1038/s41467-020-20849-y